Labile esters of agrochemicals for controlled release and reduction of off-site movement

ABSTRACT

The present invention relates to esters of carboxylic acid agrochemicals comprising a labile protecting group and having formula (I). Certain of the esters of carboxylic acid agrochemicals do not undergo hydrolysis to a significant degree in the dark, but are cleaved to regenerate the parent carboxylic acid agrochemical when exposed to light. Others of the esters of carboxylic acid agrochemicals undergo hydrolysis under both light and dark conditions. The present invention further relates to methods for the controlled release of a carboxylic acid agrochemicals, and to methods of controlling unwanted plants comprising applying to the unwanted plants an ester of a carboxylic acid agrochemical.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.15/913,030, filed on Mar. 6, 2018, which is a divisional of U.S. patentapplication Ser. No. 15/225,396, filed on Aug. 1, 2016, now abandoned,which is a divisional of U.S. patent application Ser. No. 14/351,209,filed on Apr. 11, 2014, now issued as U.S. Pat. No. 9,402,396, which isa U.S. National of PCT Application No. PCT/US2012/059792, filed Oct. 11,2012, which claims the benefit of U.S. Provisional Patent ApplicationNo. 61/545,731, filed on Oct. 11, 2011. Each of the above-citedapplications is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to the field of agrochemistry, and moreparticularly to esters of carboxylic acid agrochemicals comprising alabile protecting group. The present invention further relates tomethods for the controlled release of a carboxylic acid agrochemicals,and to methods of controlling unwanted plants comprising applying to theunwanted plants an ester of a carboxylic acid agrochemical.

BACKGROUND OF THE INVENTION

Agrochemicals are typically applied either as a solution or as asuspension of a fine powder. It is often desirable for the agrochemicalto remain either near the surface of the soil (in the case of manyinsecticides and pre-emergent herbicides, for example) or within theroot zone for active agents that are taken up through the roots, such asfertilizers and certain herbicides. However, in many cases,agrochemicals are rapidly depleted from the soil zone in which they aremost effective. Among the mechanisms of depletion are metabolism bybacteria, surface runoff and wash-down deep into the soil by rain, andvolatilization. Such depletion leads to a loss of efficacy, and can alsoresult in contamination of surface and groundwater.

One approach to extending residual activity and reducing the offsitemovement of an agrochemical involves impregnating the agrochemical intoan inert matrix. Under favorable conditions, controlled release of theagrochemical can take place. For example, U.S. Pat. No. 6,890,888describes impregnating urea and other fertilizers into expanded perlite,which can be soil-applied to achieve controlled release. Agrochemicalscan also be impregnated into clays or polymer particles, as described,for example, in U.S. Pat. No. 5,908,632 and the references citedtherein. Alternatively, an agrochemical can be chemically linked to apolymer. For example, Kenawy et al. (J. Appl. Polymer Sci. 80: 415-21(2001)) describes linking 2,4-dichlorophenoxyacetic acid (2,4-D) to apolymer backbone via an amide linkage.

For herbicides that can cause crop injury at high rate,micro-encapsulation can reduce crop injury by providing controlledrelease while reducing off-site movement. For example, Bollich et al.(Weed Technology 14:89-93 (2000)) describes micro-encapsulation ofclomazone. Several commercial microencapsulated herbicides are alsoavailable, for example, the COMMAND® (FMC Corp, clomazone) and WARRANT®(Monsanto, acetochlor) products.

Achieving controlled release is particularly challenging foragrochemicals that contain carboxylic acid groups. Such agrochemicalsare referred to herein as “carboxylic acid agrochemicals.” Carboxylicacid agrochemicals exist in the form of salts or zwitterions whenreleased in the field, rendering them water soluble. Waterborne movementof agrochemicals containing carboxylic acid groups is therefore facile.In addition, the water solubility of these compounds leads to rapidleaching from matrices which can be used for controlled release of othermolecules and complicates formation of microcapsules, a process which istypically conducted in a 2-phase, water-organic mixture with the activein the organic phase.

Alkyl esters of carboxylic acid agrochemicals exhibit reduced watersolubility. For example, as described in the Herbicide Handbook (9^(th)ed., 2007), the methyl ester of diclofop, the ethyl esters offenoxaprop-P and desmedipham, and the butyl ester of cyhalofop alongwith many alkyl esters of 2,4-D are used as herbicides. However, alkylesters of certain carboxylic acid agrochemicals hydrolyze rapidly in thesoil, rendering them more susceptible to microbial degradation. As aresult, alkyl esters of such carboxylic acid agrochemicals seldom ifever have significant residual activity. On the other hand, hinderedaromatic esters previously known in the art typically hydrolyze far tooslowly and are not practical for controlled release of agrochemicals.

Thus, there exists a need in the art for a method of achievingcontrolled release of carboxylic acid agrochemicals. This need isparticularly acute for molecules which can cause damage to crops inneighboring fields by volatilization, for example, the auxin-mimicherbicides dicamba and 2,4-D.

SUMMARY OF THE INVENTION

The present invention is directed to esters of a carboxylic acidagrochemicals comprising a photolabile or hydrolytically labileprotecting group and having the formula (I):

In formula (I), LPG is the labile protecting group, and the carboxylicacid agrochemical has the formula (II):

wherein A represents the remainder of the carboxylic acid agrochemicalbonded to the carboxylic acid moiety.

In various embodiments, the ester of a carboxylic acid agrochemical hasa photolabile group that comprises a nitrophenyl moiety. For example, insome embodiments, the ester of a carboxylic acid agrochemical has theformula (III):

wherein R is C(R₇R₈), O, or S;R₁ is C(R₉R₁₀), O, or S;provided that when R is O or S, R₁ must be C(R₉R₁₀), and when R₁ is O orS, R must be C(R₇R₈);R₇, R₈, R₉, and R₁₀ are independently H, CH₃, or CH₂CH₃;at least one of R₂ and R₃ is NO₂ and the other is H, acyclic aliphatic,amine, NO₂ or alkoxy; R₄ is H, alkoxy, acyclic aliphatic, amine, NO₂, oran ester having the formula (IV):

wherein R₁₁ is C₁-C₁₈ acyclic aliphatic;R₅ and R₆ are independently H, alkoxy, acyclic aliphatic, amine, or NO₂;provided that if any of R₂, R₃, R₄, R₅ and R₆ is acyclic aliphatic, theacyclic aliphatic does not comprise a double or triple bond between theα and β carbons;n is 0 or 1; andm is 0-3, provided that if R is O and n is 0, m is at least 1.

In other embodiments, the ester of a carboxylic acid agrochemical has aphotolabile group that comprises a phenacylmethyl ester moiety. In somesuch embodiments, the ester of a carboxylic acid agrochemical has theformula (V):

wherein R₂ is hydroxy, alkoxy, or substituted alkoxy; andR₁ and R₃ are independently H, hydroxy, alkoxy, substituted alkoxy, orC₁-C₁₈ unsubstituted or substituted acyclic aliphatic, provided that ifeither of R₁ and R₃ is C₁-C₁₈ unsubstituted or substituted acyclicaliphatic, the acyclic aliphatic does not comprise a double or triplebond between the α and β carbons.

In yet other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (VI):

wherein at least one of R and R₁ is N, and the other of R and R₁ is N orC—R₅;

R₂ is N or CH;

R₃ and R₄ are H, acyclic alkyl, substituted acyclic alkyl, or togetherform a phenyl ring;and R₅ is H, acyclic alkyl, or substituted acyclic alkyl.

In still other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (VII):

wherein R₁ and R₂ are independently H or C₁-C₈ alkyl, or together form aphenyl ring.

In various other embodiments, the ester of a carboxylic acidagrochemical has the formula (VIII):

wherein R₁, R₂, and R₃ are alkyl.

Moreover, in some embodiments, the ester of a carboxylic acidagrochemical has the formula (IX):

wherein R₁ and R₂ are halogen.

In other embodiments, the ester of a carboxylic acid agrochemical hasthe formula (X):

In yet other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (XI):

In other embodiments, the ester of a carboxylic acid agrochemical hasthe formula (XII):

wherein at least one of R₁, R₂, and R₃ is an electron-donating group;and the others of R₁, R₂, and R₃ are independently H or anelectron-donating group;provided that none of R₁, R₂, and R₃ is an electron-withdrawing group.

In still other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (XIII):

wherein at least one of R₁, R₂, and R₃ is an electron-donating group;and the others of R₁, R₂, and R₃ are independently H or anelectron-donating group;provided that none of R₁, R₂, and R₃ is an electron-withdrawing group.

In other embodiments, the ester of a carboxylic acid agrochemical hasthe formula (XIV):

wherein R is alkyl, aryl, or alkoxy;at least one of R₁, R₂, R₃, R₄, and R₅ is an electron-withdrawing group;and the others of R₁, R₂, R₃, R₄, and R₅ are independently H, alkyl,alkoxy, dialkylamino, or halogen.

In further embodiments, the ester of a carboxylic acid agrochemical hasthe formula (XV):

wherein R₁ is an electron-withdrawing group;and wherein R₂ and R₃ are independently H or alkyl.

In still further embodiments, the ester of a carboxylic acidagrochemical has the formula (XVI):

wherein R₁ is alkyl and R₂ is H, alkyl, or aryl.

In yet other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (XVII):

wherein R₁ is an electron-withdrawing group;and R₂ is H, a hydrocarbon, or an aromatic group.

In addition, in various embodiments, the ester of a carboxylic acidagrochemical is a substituted or unsubstituted aromatic ester of dicambaor 2,4-dichlorophenoxyacetic acid (2,4-D).

The present invention is further directed to agrochemical compositionscomprising any of the esters of carboxylic acid agrochemicals describedherein.

The present invention is also directed to methods for the use of theesters of carboxylic acid agrochemicals. In some embodiments, thepresent invention is directed to methods for the controlled release of acarboxylic acid agrochemical. Some such methods comprise exposing anester of a carboxylic acid agrochemical as described herein toartificial or natural light. Other of these methods comprise exposing anester of a carboxylic acid agrochemical as described herein to aqueousconditions.

In other embodiments, the present invention is directed to a method ofcontrolling unwanted plants. Such methods comprise applying to theunwanted plants an ester of a carboxylic acid agrochemical as describedherein.

In yet other embodiments, the invention relates to a method for thecontrolled release of a compound comprising exposing the compound tonatural or artificial light or exposing the compound to aqueousconditions, wherein the compound has been chemically modified to have anester linkage to a labile protecting group having one of the followingstructures:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram showing a process for the preparation of2-nitrobenzyl esters of carboxylic acid agrochemicals.

FIG. 2 is a schematic diagram showing a process for the preparation of4-methyoxyphenacylmethyl esters of carboxylic acid agrochemicals.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

It has now been discovered that certain esters of carboxylic acidagrochemicals do not undergo hydrolysis to a significant degree in thedark, but are cleaved to regenerate the parent carboxylic acid compoundwhen exposed to light. Such esters of carboxylic acid agrochemicals areof value for reducing volatility, off-site movement, and aqueoussolubility of the agrochemical. Reducing the aqueous solubility improvesresidual activity by reducing washoff and washdown into the soil andfacilitating controlled release technologies such as suspensionconcentrates and micro-encapsulation.

It has additionally been discovered that certain esters of carboxylicacid agrochemicals undergo conversion to the agronomically active acidby hydrolysis under typical agronomic conditions, while still othersundergo both hydrolysis and photolysis.

Described herein are esters of carboxylic acid agrochemicals comprisinga photolabile or hydrolytically labile protecting group having theformula (I):

In formula (I), LPG represents the labile protecting group, and thecarboxylic acid agrochemical has the formula (II):

wherein A represents the remainder of the carboxylic acid agrochemicalbonded to the carboxylic acid moiety. Some of these esters of carboxylicacid agrochemicals undergo photo-induced cleavage substantially to acarboxylic acid agrochemical of formula (II) when exposed to natural orartificial light. Others of these esters undergo hydrolytic conversionsubstantially to a carboxylic acid agrochemical of formula (II) whenexposed to moisture in the environment. These hydrolytically labileesters are suitably formulated as an emulsifiable concentrates innon-aqueous organic solvents in order to prevent premature hydrolysis.

The photolabile protecting groups of the esters of carboxylic acidagrochemicals described herein contain an aromatic moiety. The aromaticmoiety is typically somewhat hindered to prevent rapid hydrolysis of theester in the absence of light. These esters are stable to hydrolysis solong as they are not exposed to high levels of light during storage, butconvert to the agronomically active compound when exposed to natural orartificial light, for example when exposed to sunlight followingapplication of an agrochemical formulation containing the ester to afield (e.g., by spraying). Esters of formulas (III), (V), (VI) (VIII),(IX), (X), (XI), (XIII), (XIV), and (XV) undergo photolysis.

Esters of aromatic carboxylic acid agrochemicals, such as dicamba, aretypically resistant to hydrolysis under typical agronomic conditions.However, esters of carboxylic acid agrochemicals of formulas (VI),(VII), (XII), (XIV), (XV), (XVI), and (XVII) undergo hydrolysis attypical agronomic temperatures at rates (days to weeks) which providegood activity while reducing offsite movement. The esters of formulas(VI), (XIV), and (XV) undergo both hydrolysis and photolysis.

Carboxylic Acid Agrochemicals

Generally, any agrochemical that contains a carboxylic acid moiety canbe esterified to form the labile esters described herein. Thus, manydifferent types of agrochemicals can be esterified to form the labileesters. For example, the agrochemical can be a herbicide, a fungicide,an insecticide, a plant health agent, or a plant growth regulator. Othertypes of agrochemicals can also be used to form the labile esters, solong as the agrochemical has a carboxylic acid moiety.

In various embodiments, the carboxylic acid agrochemical is anauxin-mimic herbicide such as dicamba or 2,4-dichlorophenoxyacetic acid(2,4-D). For example, in certain embodiments of the present invention,the ester of a carboxylic acid agrochemical is a substituted orunsubstituted aromatic ester of dicamba or 2,4-D.

Suitable herbicides also include, but are not limited to fenoxaprop,fenoxaprop-P, desmedipham, cyhalofop, carfentrazone, flufenpyr,fluthiacet, fluroglycofen, pyraflufen, flumiclorac,4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB), fluroxypyr, picloram,quinclorac, benazolin, clodinafop, 4-(2,4-dichlorophenoxy)butanoic acid(2,4-DB), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), dichlorprop,dichlorprop-P, diethatyl, endothall, fluazifop, flufenpyr, flumiclorac,fluoroglycofen, haloxyfop, indole-3-acetic acid, indole-3-butyric acid,mecoprop, mecoprop-P, pyrafluren, fenoprop, triclopyr, aminopyralid,bispyribac, chlorthal, imazamethabenz, pyrothiobac, quinmerac,quizalofop, quizalofop-P, diclofop, and lactofen. The structure oflactofen includes an ethyl ester which is hydrolyzed rapidly in situ toform the active form of the herbicide. The term “lactofen” as usedherein refers to the active form of the herbicide, which includes acarboxylic acid moiety.

Suitable fungicides include, but are not limited to, benalaxyl andpicoxystrobin. The terms “benalaxyl” and “picoxystrobin” are used in theart to refer to both the active forms of the compounds, which includecarboxylic acid moieties, and to the methyl esters of the compounds. Asused herein, the terms “benalaxyl” and “picoxystrobin” refer to theactive forms of the compounds.

Suitable plant health agents include, but are not limited to, salicylicacid and 3,6-dichlorosalicylic acid. Suitable plant growth regulatorsinclude, but are not limited to cloprop and 4-chlorophenoxyacetic acid(4-CPA).

Typically, the labile esters are esters of agrochemicals that contain anaromatic carboxylic acid (e.g., dicamba). Aromatic carboxylic acids aremore resistant to hydrolysis, thus providing better control of therelease rate.

Although the following description of the labile esters and theirsynthesis, formulation, and use focuses on esters of dicamba and 2,4-D,the person having ordinary skill in the art will recognize that the sameprinciples and methodology are applicable to other carboxylic acidagrochemicals.

Esters of Carboxylic Acid Agrochemicals Comprising a Labile ProtectingGroup

A. Nitrophenyl Esters

Several classes of esters of carboxylic acid agrochemicals have beenfound to undergo photo-induced cleavage to form the agronomically activecarboxylic acid agrochemical when exposed to natural or artificiallight. The first of these classes are the nitrophenyl esters. In thenitrophenyl esters, the photolabile protecting group of the ester of acarboxylic acid agrochemical comprises a nitrophenyl moiety. Thesenitrophenyl esters of carboxylic acid agrochemicals typically have theformula (III):

whereinR is C(R₇R₈), O, or S;R₁ is C(R₉R₁₀), O, or S;provided that when R is O or S, R₁ must be C(R₉R₁₀), and when R₁ is O orS, R must be C(R₇R₈);R₇, R₈, R₉, and R₁₀ are independently H, CH₃, or CH₂CH₃;at least one of R₂ and R₃ is NO₂ and the other is H, acyclic aliphatic,amine, NO₂ or alkoxy;R₄ is H, alkoxy, acyclic aliphatic, amine, NO₂, or an ester having theformula (IV):

wherein R₁₁ is C₁-C₁₈ acyclic aliphatic;R₅ and R₆ are independently H, alkoxy, acyclic aliphatic, amine, or NO₂;provided that if any of R₂, R₃, R₄, R₅ and R₆ is acyclic aliphatic, theacyclic aliphatic does not comprise a double or triple bond between theα and β carbons;n is 0 or 1; andm is 0-3, provided that if R is O and n is 0, m is at least 1.

The nitrophenyl esters contain a nitrophenyl group linked to the oxygenof the carboxylate moiety by a chain that typically comprises no morethan five bonds in the main chain (i.e., exclusive of any branching).Typically, the nitrophenyl esters are 2-nitrophenyl esters, but3-nitrophenyl esters have also been found to undergo photolysis. Thus,in various embodiments, R₂ is NO₂. In other embodiments, R₃ is NO₂.

The chain linking the nitrophenyl group to the carboxylate typicallycomprises two to five bonds in the main chain, and may also comprise oneor more alkyl branches. The linker chain typically comprises carbon,oxygen, and/or sulfur atoms, and more typically comprises carbon andoxygen atoms. Thus, in various embodiments, R is C(R₇R₈) or oxygen. Ifthe linker chain comprises one or more alkyl branches, the alkylbranches are typically methyl or ethyl. In certain embodiments, it ispreferred that there are no branches or one branch at any given carbonatom in the linker chain. Thus, for example, in various embodiments, Ris C(R₇R₈) and one of R₇ and R₈ is H and the other is H, CH₃, or CH₂CH₃.Similarly, in various other embodiments, R₁ is C(R₉R₁₀) and one of R₉and R₁₀ is H and the other is H, CH₃, or CH₂CH₃. In some otherembodiments, the chain linking the nitrophenyl group to the carboxylatedoes not have any branching. For example, in some embodiments, R isC(R₇R₈) and R₇ and R₈ are both H.

In some embodiments, the linker chain is unbranched and comprises aC₁-C₄ alkyl chain. For example, in various embodiments, R is C(R₇R₈), R₇and R₈ are both H, n is 0, and m is 0, and the linker chain thuscomprises a single CH₂ moiety. In other embodiments, R is C(R₇R₈); R₁ isC(R₉R₁₀); R₇, R₈, R₉, and R₁₀ are all H; n is 1; and m is 0. In theseembodiments, the linker chain comprises a C₂ alkyl moiety. In yet otherembodiments, R is C(R₇R₈), R₇ and R₈ are both H, n is 0, and m is 1-3,and the linker chain comprises a C₂-C₄ alkyl moiety.

In still other embodiments, the linker chain comprises an oxygen orsulfur atom. In some embodiments, R is C(R₇R₈) and R₁ is O. In otherembodiments, R is O and R₁ is C(R₉R₁₀). For example, in variousembodiments, R is C(R₇R₈), R₇ and R₈ are both H, R₁ is O, n is 1, and mis 2. In various other embodiments, R is O, R₁ is C(R₉R₁₀), R₉ and R₁₀are both H, n is 1, and m is 1.

In addition to the nitro group(s) that must be present at one or both ofthe 2- and 3-positions, the nitrophenyl esters may also have additionalsubstituents on the phenyl ring. For example, in some embodiments, atleast one of R₂, R₃, R₄, R₅, and R₆ is acyclic aliphatic. However, ifany of R₂, R₃, R₄, R₅, and R₆ is acyclic aliphatic, it is preferred thatthe acyclic aliphatic does not comprise a double or triple bond betweenthe α and β carbons. In embodiments where at least one of R₂, R₃, R₄,R₅, and R₆ is acyclic aliphatic, the acyclic aliphatic typically isC₁-C₁₈ acyclic aliphatic, and more typically C₁-C₁₈ alkyl.

In various other embodiments, at least one of R₂, R₃, R₄, R₅, and R₆ isalkoxy. In such embodiments, the alkoxy is typically C₁-C₁₈ alkoxy, forexample methoxy. In some embodiments, both of R₄ and R₅ are alkoxy, forexample methoxy.

In yet other embodiments, at least one of R₂, R₃, R₄, R₅, and R₆ isamine. In such embodiments, the amine may be NH₂ or a substituted amine.If the amine is a substituted amine, it is preferred that there is notan amide at the ring position adjacent to the nitro group, because suchan amide would be susceptible to photocleavage.

Particular examples of nitrophenyl esters of carboxylic acidagrochemicals of formula (III) include compounds wherein:

-   -   R₂ is NO₂; each of R₃, R₄, R₅, and R₆ is H; R is C(R₇R₈); R₇ and        R₈ are both H; n is 0; and m is 0;    -   R₂ is NO₂, each of R₃ and R₆ is H, each of R₄ and R₅ are        methoxy, R is C(R₇R₈), R₇ and R₈ are both H, n is 0, and m is 0;    -   R₃ is NO₂; each of R₂, R₄, R₅, and R₆ is H; R is C(R₇R₈); R₇ and        R₈ are both H; n is 0; and m is 0;    -   R₂ is NO₂; each of R₃, R₄, R₅, and R₆ is H; R is C(R₇R₈); R₁ is        C(R₉R₁₀); R₇, R₈, R₉, and R₁₀ are all H; n is 1; and m is 0;    -   R₂ is NO₂; each of R₃, R₄, R₅, and R₆ is H; R is O; R₁ is        C(R₉R₁₀); R₉ and R₁₀ are both H; n is 1; and m is 1; or    -   R₂ is NO₂; each of R₃, R₄, R₅, and R₆ is H; R is C(R₇R₈); R₇ and        R₈ are both H; R₁ is O, n is 1, and m is 2.

Thus, where the carboxylic acid agrochemical is dicamba, particularexamples of the nitrophenyl esters of formula (III) include thefollowing compounds:

The 2-nitrobenzyl (1a) and 2-nitrophenethyl (2) esters of dicamba canreadily be prepared by esterification with the parent alcohol or, in thecase of the 2-nitrobenzyl ester, by halide displacement from2-nitrobenzyl chloride or 2-nitrobenzyl bromide. Syntheses for thesecompounds are described in the Examples below.

The solubility of the nitrophenyl esters in organic solvents increasesas the length of the linker chain increases, and this increasedsolubility enables higher loading to be achieved in emulsifiableconcentrate formulations. However, for nitrophenyl esters having linkerscomprising more than two atoms (for example, compounds 3 and 4 above)the rate of photolysis decreases. A compound such as compound 2 would besuitable for emulsifiable concentrate formulations intended forpost-emergent weed control. On the other hand, a compound such ascompound 1a would be suitable for suspension concentrate or wettablegranule formulations due to its higher melting point and lower cost.

It has also been discovered that analogs of 1a, such as 1b and 1c, arealso effective herbicides. Compound 1b, the 6-nitroveratryl ester ofdicamba, is significantly less soluble than 1a and is therefore bettersuited to suspension concentrates. Compound 1c, the 3-nitrobenzyl esterof dicamba, undergoes slower and less efficient photolysis than the2-nitrobenzyl ester, 1a.

Field tests of emulsifiable concentrates of compounds 1a and 2 showedthem to be slightly more effective than the diglycolamine salt ofdicamba for control of broadleaf weeds. Similar activity was seen ingreenhouse tests of post-emergent control of velvetleaf, described infurther detail in the Examples below. Without being bound to anyparticular theory, the somewhat better performance in the field isthought to be due to the availability of ultraviolet light outdoors.Thus, compounds 1a and 2 are particularly suitable for post-emergentcontrol of broadleaf weeds, especially where minimizing off-sitemovement is a priority.

In other embodiments, the carboxylic acid agrochemical is 2,4-D. In suchembodiments, particular examples of the nitrophenyl esters of formula(III) include the following compounds:

B. Phenacylmethyl Esters

Another class of esters of carboxylic acid agrochemicals that have beenfound to undergo photo-induced cleavage to form the agronomically activecarboxylic acid agrochemical when exposed to natural or artificial lightare the phenacylmethyl esters. This class of esters includes esters ofcarboxylic acid agrochemicals comprising a photolabile protecting groupwhich includes a phenacylmethyl ester moiety. The phenacylmethyl esterstypically have the formula (V):

wherein R₂ is hydroxy, alkoxy, or substituted alkoxy; andR₁ and R₃ are independently H, hydroxy, alkoxy, substituted alkoxy, orC₁-C₁₈ unsubstituted or substituted acyclic aliphatic, provided that ifeither of R₁ and R₃ is C₁-C₁₈ unsubstituted or substituted acyclicaliphatic, the acyclic aliphatic does not comprise a double or triplebond between the α and β carbons.

In various embodiments, at least one of R₁, R₂, and R₃ is alkoxy orsubstituted alkoxy. In such embodiments, the alkoxy or substitutedalkoxy can have the formula: —O—CH₂—R₄, wherein R₄ is H, C₁-C₁₇unsubstituted or substituted acyclic aliphatic, an amine, an aliphaticamine, an aliphatic diamine, a carboxylic acid, a sulfonic acid,hydroxy, an aliphatic ring, or an aromatic ring.

For example, in some embodiments, R₂ is alkoxy and R₁ and R₃ are both H.In various other embodiments, R₂ is hydroxy and R₁ and R₃ are both H.

Particular examples of phenacylmethyl esters of formula (V) includecompounds wherein R₂ is methoxy or n-butoxy, and R₁ and R₃ are both H.For example, where the carboxylic acid agrochemical is dicamba,particular examples of the phenacylmethyl esters of formula (V) includethe following compounds.

The 4-methoxyphenacyl methyl ester of dicamba (9) and the analogous4-n-butoxyphenacyl methyl ester (10) can readily be prepared fromdicamba in high yield, as described below in the Examples. Both of thesecompounds undergo photo-release to release dicamba. In vitro studiesdescribed below in the Examples indicate that the photo-efficiency ofdicamba generation from compound 9 is virtually 100%. Compound 9 isrelatively insoluble and is best suited for use in suspensionconcentrates; however, an emulsifiable concentrate of 9 inmonochlorobenzene was shown to be effective for post-emergent control ofbroadleaf weeds, as described in the Examples below. It has also beenfound that efficient photo-release of 9 in a suspension concentrateformulation occurs over several weeks, further demonstrating the abilityof 9 to provide extended pre-emergent weed control.

Compound 10 is a liquid at room temperature and is also effective forpost-emergent broadleaf weed control when formulated as an emulsifiableconcentrate, as described in the Example below.

In other embodiments, the carboxylic acid agrochemical is 2,4-D. In suchembodiments, particular examples of the phenacylmethyl esters of formula(V) include the following compounds:

C. Other Esters

It has further been discovered that certain other aromatic esters ofcarboxylic acid agrochemicals also provide for efficient release of anactive agrochemical. For example, in various embodiments, the esters ofthe carboxylic acid agrochemicals have the formula (VI):

wherein at least one of R and R₁ is N, and the other of R and R₁ is N orC—R₅;

R₂ is N or CH;

R₃ and R₄ are H, acyclic alkyl, substituted acyclic alkyl, or togetherform a phenyl ring;and R₅ is H, acyclic alkyl, or substituted acyclic alkyl.

In the esters of carboxylic acid agrochemicals of formula (VI), one orboth of R and R₁ are nitrogen. It has been discovered that compoundshaving a nitrogen atom at one or both of these positions achieveefficient release of the agrochemical. Such release generally occursthrough hydrolysis, although photolysis can also contribute. Compoundsof formulas VII, XII, and XIII, discussed below, also havenitrogen-containing aromatic rings and undergo hydrolysis under typicalagronomic conditions. Without being bound to any particular theory, itis believed that a ring nitrogen atom adjacent to the phenolic carbon ofthe ester stabilizes adducts with water or hydroxide by a mechanismsimilar to that shown below for the 2-hydroxypyridine ester of dicamba:

As described below, some esters of this type, such as the 2-quinoxalinolester of dicamba, also under photolysis to yield the carboxylic acidagrochemical. Without being bound to any particular theory, it isbelieved that in the case of photolysis, the nitrogen atoms at the Rand/or R₁ positions serve two functions: (1) blocking sites α to theester in order to prevent recombination and ketone formation afterphoto-induced cleavage of the ester; and (2) inhibiting recombination byenabling the aromatic hydroxy group to tautomerize to the keto form,preventing recombination.

In various embodiments of the esters of carboxylic acid agrochemicals offormula (VI), R₁ is C—R₅ and R₅ is H, alkyl (e.g., methyl), orsubstituted alkyl.

In addition, in various embodiments, R₂ can also be nitrogen. In otherembodiments, R₂ is CH.

In the esters of carboxylic acid agrochemicals of formula (VI), R₃ andR₄ are H, acyclic alkyl, substituted acyclic alkyl, or together form aphenyl ring. Typically, R₃ and R₄ are both H or together form a phenylring.

In various embodiments of the esters of carboxylic acid agrochemicals offormula (VI), at least one of R₃, R₄, and R₅ is C₁-C₁₈ acyclic alkyl orC₁-C₁₈ substituted acyclic alkyl.

The C₁-C₁₈ substituted acyclic alkyl can be substituted with, forexample, one or more hydroxy groups or one or more sulfonic acid groups.

Particular examples of the esters of carboxylic acid agrochemicals offormula (VI) include compounds wherein:

R and R₂ are N; R₁ is C—R₅; R₃ and R₄ together form a phenyl ring; andR₅ is H;

R and R₂ are N; R₁ is C—R₅; R₃ and R₄ together form a phenyl ring; andR₅ is methyl; or

R is N; R₁ is C—R₅; R₂ is CH; and R₃, R₄, and R₅ are all H.

Thus, for example, where the carboxylic acid agrochemical is dicamba,particular examples of the esters of carboxylic acid agrochemicals offormula (VI) include the following compounds:

A proposed scheme for the photo release of dicamba from the2-quinoxalinol ester 13a is shown below:

Although the mechanistic detail in this scheme is not firmlyestablished, the outstanding efficacy of the photo andhydrolytically-labile 2-quinoxalinol protecting group is shown in theExamples below.

When used as an emulsifiable concentrate, the 2-quinoxalinol ester ofdicamba, 13a, has similar post-emergent activity for control ofbroadleaf weeds as the diglycolamine salt of dicamba, while exhibitingsuperior extended pre-emergent control of Palmer amaranth at 21 and 44days after treatment. The 2-hydroxypyridine ester 14 also undergoesefficient cleavage to form dicamba, as shown in the Examples below.Ester 14 is readily soluble in organic solvents and can be formulated asan emulsifiable concentrate or a suspension concentrate.

In other embodiments, the carboxylic acid agrochemical is 2,4-D. In suchembodiments, particular examples of the esters of formula (VI) includethe following compounds:

In other various embodiments, the ester is a diester of a carboxylicacid agrochemical having the formula (VII):

wherein R₁ and R₂ are independently H or C₁-C₈ alkyl, or together form aphenyl ring. R₁ and R₂ are typically both H, or together form a phenylring.

In various embodiments, the carboxylic acid agrochemical is dicamba, andexamples of the diesters of formula (VII) include the followingcompounds:

Like the esters of formula VI, the esters of formula VII generallyrevert to the parent carboxylic acid by hydrolysis rather than byphotolysis. The maleic hydrazide and phthalhydrazide diesters (17 and18) undergo efficient cleavage to form dicamba. The phthalhydrazidediester, 18, is highly insoluble and is preferably formulated as asuspension concentrate. The maleic hydrazide diester, 17, is readilysoluble in organic solvents and can be formulated as an emulsifiableconcentrate or a suspension concentrate.

In various other embodiments, the carboxylic acid agrochemical is 2,4-D,and examples of the diesters of formula (VII) include the followingcompounds:

In yet other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (VIII):

wherein R₁, R₂, and R₃ are alkyl.

In the esters of formula (VIII), the substitutions ortho and para to theester block ketone formation. Typically, at least one of the orthosubstituents is branched to prevent recombination of the phenol and acylphoto-fragments. For example, an isopropyl or tertiary butyl substituentcan be present at the ortho position. Thus, typically at least one of R₁and R₃ is branched alkyl, e.g., isopropyl or t-butyl.

In addition, in various embodiments of the esters of formula (VIII), atleast one of R₁ and R₂ is methyl. As one example, in a particularembodiment R₁ and R₂ are both methyl and R₃ is t-butyl. Where thecarboxylic acid agrochemical is dicamba, this ester of formula (VIII)has the following structure:

Ester 21 has been shown to undergo photo-release of dicamba in vitro. Inaddition, the substituted phenol byproducts formed upon photo-release ofthe agrochemical from the esters of formula (VIII) are effectiveanti-oxidants and can provide plant health benefits under somecircumstances.

In other embodiments of the esters of formula (VIII), the carboxylicacid agrochemical is 2,4-D. Thus, for example, an ester of formula(VIII) can have the following structure:

In yet other various embodiments, a phenolic agrochemical can beincorporated into the photolabile ester of a carboxylic acidagrochemical, thereby affording a photo-labile ester which providesphoto-release of two different agrochemicals that may have differentmodes of action. In some such embodiments, the ester of a carboxylicacid agrochemical has the formula (IX):

wherein R₁ and R₂ are halogen.

In the esters of formula (IX), the phenolic agrochemical is typicallychloroxynil, bromoxynil, or ioxynil. Thus, typically, R₁ and R₂ are bothchloro (where the phenolic agrochemical is chloroxynil), R₁ and R₂ areboth bromo (where the phenolic agrochemical is bromoxynil), or R₁ and R₂are both iodo (where the phenolic agrochemical is ioxynil). Thechloroxynil, bromoxynil, and ioxynil esters of dicamba have thefollowing structures:

The chloroxynil, bromoxynil and ioxynil esters of dicamba (23a, 23b, and23c) provide photo-release of dicamba and an herbicide with a secondmode of action. Chloroxynil, bromoxynil, and ioxynil esters can also beused to provide photo-release of other carboxylic acid agrochemicals.For example, the chloroxynil, bromoxynil, and ioxynil esters of 2,4-Dhave the following structures:

Similarly, the fungicide quinolinol can be used to form a photo-labileester of a carboxylic acid agrochemical. In such embodiments, the esterof a carboxylic acid agrochemical has the formula (X):

For example, the quinolinol esters of dicamba and 2,4-D have thefollowing structures:

In other embodiments, the herbicide medinoterb can be used to form aphoto-labile ester of a carboxylic acid agrochemical. In suchembodiments, the ester of a carboxylic acid agrochemical has the formula(XI):

For example, the medinoterb esters of dicamba and 2,4-D have thefollowing structures:

D. Activated Benzylic Esters

In some embodiments, the ester of a carboxylic acid agrochemical has theformula (XII):

wherein at least one of R₁, R₂, and R₃ is an electron-donating group;and the others of R₁, R₂, and R₃ are independently H or anelectron-donating group;provided that none of R₁, R₂, and R₃ is an electron-withdrawing group.

Suitable electron-donating groups include alkoxy (e.g. methoxy), alkyl,amino, alkylamino, and dialkylamino.

In embodiments wherein the electron-donating group is alkyl, alkylamino,or dialkylamino the alkyl is typically C₁-C₁₈ alkyl.

In embodiments wherein the electron-donating group is alkoxy, the alkoxyis typically C₁-C₁₈ alkoxy. For instance, in certain embodiments, atleast one of R₁, R₂, and R₃ is methoxy. For example, in someembodiments, R₂ is methoxy and R₁ and R₃ are both H. Where thecarboxylic acid agrochemical is dicamba, this ester of formula (XII) hasthe following structure:

In other embodiments of the esters of formula (XII), the carboxylic acidagrochemical is 2,4-D. Where the carboxylic acid agrochemical is 2,4-D,a particular example of a compound of formula (XII) has the followingstructure:

Unactivated benzylic esters of aromatic carboxylic acids such as dicambaare resistant to hydrolysis under typical agronomic conditions. However,activated benzylic esters of formula (XII), particularly thosecontaining alkoxy or dialkylamino groups in the ortho or para position,undergo hydrolysis by the mechanism shown below, in which elimination ofthe dicamba anion occurs directly followed by hydrolysis of thestabilized benzylic cation. The 4-methoxybenzyl ester of dicamba, 29a,is suitable for the fast release of dicamba. Such rapid hydrolysis isuseful in dry soil (which slows the rate of hydrolysis) or when physicalmethods such as encapsulation are used to govern the rate of esterrelease to the environment.

E. Activated Phenolic Esters

In still other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (XIII):

wherein at least one of R₁, R₂, and R₃ is an electron-donating group;and the others of R₁, R₂, and R₃ are independently H or anelectron-donating group;provided that none of R₁, R₂, and R₃ is an electron-withdrawing group.

Suitable electron-donating groups include alkoxy (e.g., methoxy), alkyl,amino, alkylamino, and dialkylamino.

In embodiments wherein the electron-donating group is alkyl, alkylamino,or dialkylamino the alkyl is typically C₁-C₁₈ alkyl.

In embodiments wherein the electron-donating group is alkoxy, the alkoxyis typically C₁-C₁₈ alkoxy. For instance, in certain embodiments, atleast one of R₁, R₂, and R₃ is methoxy. For example, in someembodiments, R₂ is methoxy and R₁ and R₃ are H. Where the carboxylicacid agrochemical is dicamba, this ester of formula (XIII) has thefollowing structure:

In other embodiments of the esters of formula (XIII), the carboxylicacid agrochemical is 2,4-D. Where the carboxylic acid agrochemical is2,4-D, a particular example of a compound of formula (XIII) has thefollowing structure:

Methoxy and dialkylamino groups promote the photolysis of phenolicesters of carboxylic acid agrochemicals by a mechanism similar to thatby which they promote hydrolysis of benzylic esters. In both cases, theeffect is to promote the elimination of the carboxylate anion and astabilized cation, as shown below for the 4-methoxyphenyl ester ofdicamba, 30a. Thus esters of structural formula (XIII) undergophoto-release of carboxylic acids. Photo-release is significantly slowerthan for esters of formula (III) or (V), providing further suppressionof volatility and a more extended release of the active agrochemical.

F. Benzylic Esters Prepared by the Baylis-Hillman Reaction

In other embodiments, the ester of a carboxylic acid agrochemical is abenzylic ester having the formula (XIV):

wherein R is alkyl, aryl, or alkoxy;at least one of R₁, R₂, R₃, R₄, and R₅ is an electron-withdrawing group;and the others of R₁, R₂, R₃, R₄, and R₅ are independently H, alkyl,alkoxy, dialkylamino, or halogen.

Suitable electron withdrawing groups include nitro, ester, andsulfonate. Thus, for example, in certain compounds of formula (XIV), atleast one of R₁, R₂, R₃, R₄, and R₅ is nitro.

In embodiments wherein one or more of R, R₁, R₂, R₃, R₄, and R₅ isalkyl, the alkyl is typically C₁-C₁₈ alkyl. Thus, for example, in someembodiments, one or more of R, R₁, R₂, R₃, R₄, and R₅ is methyl orethyl.

When one or more of R, R₁, R₂, R₃, R₄, and R₅ is alkoxy, the alkoxy issuitably C₁-C₁₈ alkoxy (e.g., methoxy or ethoxy).

Typical R substituents include methyl, ethyl, substituted phenoxy, andC₁-C₁₈ alkoxy. For example, in certain embodiments, R is ethoxy.

Particular examples of esters of formula (XIV) include compoundswherein:

R is ethoxy, R₁ is nitro, and each of R₂, R₃, R₄, and R₅ are H;

R is ethoxy, R₂ is nitro, and each of R₁, R₃, R₄, and R₅ are H; or

R is ethoxy, R₃ is nitro, and each of R₁, R₂, R₄, and R₅ are H.

Thus, where the carboxylic acid agrochemical is dicamba, particularexamples of the esters of formula (XIV) include the following compounds:

In other embodiments of the esters of formula (XIV), the carboxylic acidagrochemical is 2,4-D. For such embodiments, particular examples of theesters of formula (XIV) include the following compounds:

Hydrolytically labile esters of aromatic carboxylic acids of formula(XIV) can be conveniently prepared via the Baylis-Hillman reactionfollowed by esterification with the carboxylic acid agrochemical. TheBaylis-Hillman reaction is reviewed in Drewes S. E., Roos G. H. P.,“Synthetic Potential of the Tertiary Amine-Catalysed Reaction ofActivated Vinyl Carbanions with Aldehyde,” Tetrahedron, 1988, 44,4653-70) and Basavaiah, D., Rao, P. D., Hyma, R. S., “The Baylis-HillmanReaction: A Novel Carbon-Carbon Bond Forming Reaction,” Tetrahdedron,1996, 8001-62. The parent alcohols of the present invention are obtainedby reaction of a vinyl compounds with an electron-withdrawing group anda substituted benzaldehyde catalyzed by a tertiary amine, preferablydiazabicyclo[2,2,2] octane, commonly known as “DABCO” or quinuclidine.Suitable benzaldehydes include nitrobenzaldehydes, particularly whensubstituted in an ortho orientation. Suitable vinyl compounds includevinyl esters, particularly ethyl acrylate.

The synthesis of a typical parent alcohol by the Baylis-Hillman pathwayis shown below. The dicamba ester of this alcohol is designatedstructure 31a. Two related structures, 31b and 31c, shown above, arealso useful for controlled release of dicamba. Laboratory syntheticprocedures for esters 31a, 31b, and 31c are given below in the Examples,using reaction times of several days at room temperature. Forlarger-scale production, it is suitable to conduct the reactions atelevated pressure, which greatly accelerates the rate of theBaylis-Hillman reaction, as described in the literature (Hill, J. S.,Isaacs, N. S., Tetr. Lett., 1986, 5007.)

The Baylis-Hillman synthesis represents a high yield conversion oflow-cost benzaldehydes to benzylic alcohols. In addition, the carbonylgroup introduced beta to the benzylic carbon renders the agrochemicalester more hydrolytically labile. The rate of hydrolysis can be enhancedby adding activating groups such as methoxy or dialkylamino to the orthoor para positions of the aromatic ring or conversely reduced by theaddition of electron-withdrawing groups such as esters, sulfonates, ornitro groups. Moreover, when a nitro group is present on the ring alphato the benzylic position, the ester is rendered photo-labile.

G. Esters Obtained by Michael Addition of Activated Olefins to MaleicHydrazide

In further embodiments, the ester of a carboxylic acid agrochemical hasthe formula (XV):

wherein R₁ is an electron-withdrawing group;and wherein R₂ and R₃ are independently H or alkyl.

Suitable electron-withdrawing groups include, for example, nitriles,ketones, aldehydes, esters, carboxylates, and nitro.

In some embodiments of the compounds of formula (XV), both R₂ and R₃ areH. In other embodiments, one or both of R₂ and R₃ are alkyl, typicallyC₁-C₁₈ alkyl.

Particular examples of carboxylic acid agrochemicals of formula (XV)include compounds wherein:

R₁ is —COCH₃ and R₂ and R₃ are both H;

R₁ is —CH═O and R₂ and R₃ are both H; or

R₁ is —CN and R₂ and R₃ are both H;

R₁ is —COOCH₂CH₃ and R₂ and R₃ are both H.

Thus, where the carboxylic acid agrochemical is dicamba, particularexamples of the esters of formula (XV) include the following compounds:

In other embodiments of the esters of formula (XV), the carboxylic acidagrochemical is 2,4-D. For such embodiments, particular examples of theesters of formula (XV) include the following compounds:

The useful class of esters of structural formula (XV) is obtained byforming an ester of a carboxylic acid agrochemical with an alcoholobtained by base-catalyzed Michael addition of maleic hydrazide to vinylcompounds activated with electron-withdrawing groups. Esters 32a, 33aand 34a, shown above, are obtained by Michael addition of methyl vinylketone, acrolein, and acrylonitrile, respectively to maleic hydrazide.The dicamba esters of the Michael adducts can release dicamba byhydrolysis (since there is a nitrogen alpha to the ester linkage) or acombination of hydrolysis and photolysis. The utility of esters offormula (XV) is also due to the fact that the physical properties of theester can be modified. Ester 34a is an insoluble solid which can beformulated as a suspension concentrate while esters 32a and 33a areeffectively room-temperature liquids (although 32a undergoes somecrystallization over a period of weeks) and can be formulated ashigh-loading emulsifiable concentrates. The synthesis of these esters isdescribed in the Examples.

H. Di-Alkylated Hydroxypyridine Esters of Carboxylic Acid Agrochemicals

In still further embodiments, the ester of a carboxylic acidagrochemical has the formula (XVI):

wherein R₁ is alkyl and R₂ is H, alkyl, or aryl.

The compounds of formula (XVI) are symmetrically substituted with alkylgroups at the R₁ positions. R₁ is typically C₁-C₁₈ alkyl. For example,in some esters of formula (XVI), R₁ is tertiary-butyl.

In some embodiments, R₂ is H. In other embodiments, R₂ is alkyl,typically C₁-C₁₈ alkyl. In still other embodiments, R₂ is aryl. When R₂is aryl, the aromatic ring optionally contains nitrogen and isoptionally substituted with up to three C₁-C₁₈ alkyl groups.

In a particular example of an ester of a carboxylic acid agrochemical offormula (XVI), R₁ is tertiary-butyl and R₂ is H. Thus, where thecarboxylic acid agrochemical is dicamba, a particular example of acompound of formula (XVI) has the structure:

In other embodiments of the esters of formula (XVI), the carboxylic acidagrochemical is 2,4-D. Where the carboxylic acid agrochemical is 2,4-D,a particular example of a compound of formula (XVI) has the followingstructure:

The solubility of the 2-hydroxypyridine ester of dicamba (compound 14)and other carboxylic acid agrochemicals can be improved and the activitymodulated by symmetrical substitution of the ring with alkyl groups (R₁in formula XVI). A convenient synthetic route involving condensation ofbeta-diketones with 2-cyanoacetamide also adds a nitrile group to thering. A typical ester of formula (XVI) is the dicamba ester designatedcompound 36a, where R₁ is tertiary butyl and R₂ is hydrogen. Thesynthesis and activity of 36a are described in the Examples.

I. Pyridine Diesters of Carboxylic Acid Agrochemicals

In yet other embodiments, the ester of a carboxylic acid agrochemicalhas the formula (XVII):

wherein R₁ is an electron-withdrawing group;and R₂ is H, a hydrocarbon, or an aromatic group.

Suitable electron-withdrawing groups include, for example, cyano,carboxylalkyl, aldehyde, and nitro. In certain embodiments, R₁ is cyano.Where R₁ is carboxyalkyl, the alkyl is typically C₁ to C₁₂ alkyl.

In some embodiments of the esters of formula (XVII), R₂ is H. In otherembodiments, R₂ is a hydrocarbon. Suitable hydrocarbons include C₁-C₁₈alkyl. In still other embodiments, R₂ is an aromatic group. The aromaticring optionally contains nitrogen and is optionally substituted with upto three C₁-C₁₈ alkyl groups. In certain embodiments, R₂ is phenyl.

In a particular example of an ester of a carboxylic acid agrochemical offormula (XVII), both R₁ is cyano and R₂ is phenyl. Thus, where thecarboxylic acid agrochemical is dicamba, a particular example of acompound of formula (XVII) has the structure:

In other embodiments of the esters of formula (XVII), the carboxylicacid agrochemical is 2,4-D. Where the carboxylic acid agrochemical is2,4-D, a particular example of a compound of formula (XVII) has thefollowing structure:

The liquid, hydrolytically labile esters of carboxylic acidagrochemicals of formula (XVII) can be obtained by a method involvingthe double Knoevagel condensation of an aldehyde with two equivalents of2-cyanoacetamide, yielding a nucleus with two phenolic groups which canbe esterified, both adjacent to a ring nitrogen which sensitizes theester to hydrolysis. A general outline of the synthesis is shown below.Two equivalents of 2-cyanoacetamide are condensed with an aldehyde underbasic conditions which is followed, without isolation, by ring closureunder neutral conditions. Ring oxidation is facile in the presence ofair or other oxidants.

A useful example of esters of formula (XVII) is the ester designated 37a(shown above). Its synthesis and hydrolysis under typical agronomicconditions are described in the Examples.

Synthesis of the Esters of Carboxylic Acid Agrochemicals

As explained in greater detail in the Examples below, the esters of thepresent invention can be prepared by esterification of the appropriatealcohol with the carboxylic acid agrochemical or reaction of the acidchloride of the agrochemical with the alcohol. The use of dimethylaminopyridine (“DMAP”) improves reaction rates and yields when using the acidchloride route, as illustrated in the Examples below for dicamba and2,4-D esters.

Photo-labile esters of 2,4-D can be prepared similarly to the dicambaesters. Most esters are easily prepared from the acid chloride of 2,4-D.2,4-D acid chloride and ester synthesis is described in M. S. Newman, etal., J. Am. Chem. Soc. 69:718-23 (1947). The synthesis of the 2,4-Desters 5a, 11, and 15a is described in the Examples below.

Thus, the esters of the present invention can be prepared from the acidchloride of dicamba, 2,4-D and other herbicides. The acid chloride isalso a convenient intermediate to other esters of the present invention.

The 2-nitrobenzyl esters of dicamba (1) and 2,4-D (5a) are economicallyprepared from the reaction of 2-nitrobenzyl chloride with dicamba or2,4-D in the presence of a base as described in Example 4 below. Thebases are typically organic amines, particularly triethylamine. It hasbeen found that use of a slightly substoichiometric amount of baserelative to dicamba or 2,4-D is preferred as this prevents reaction offree amine with 2-nitrobenzyl chloride.

A typical process for the preparation of 1a is illustrated in FIG. 1.The process can be performed continuously or semi-continuously, but ineither case the amine base is regenerated by reaction with a strongaqueous base such as sodium hydroxide and is recycled along withunreacted starting materials and ester that has not precipitated. Thismethod is also applicable to the 2-nitrobenzyl ester of 2,4-D, 5a.Preferably, an excess of 2-nitrobenzyl chloride is present in thereaction mixture and a polar, hydrophobic solvent such a methylenechloride or 1,2-dichlorobenzene is utilized. 2-nitrobenzyl bromide canalso be used in this process, as described in Example 14.

2-nitrobenzyl chloride is typically prepared by chlorination of2-nitrotoluene. Selective monochlorination of toluene at partialconversion is known and is described in Chlorotoluenes, in Kirk-OthmerEncyclopedia of Chemical Technology (5th ed. 2004). An alternativesynthetic method is o-nitration of benzyl chloride, but para nitrationalso occurs, reducing yield.

A similar process can be used for the synthesis of the4-methoxyphenacylmethyl esters 9 and 11. FIG. 2 illustrates this processfor the 4-methoxyphenacylmethyl ester of dicamba (9). The primarydifference is that 4-methoxy-α-chloroacetophenone is reacted with thecarboxylate. As described in Example 8, this intermediate isconveniently prepared by Friedel Crafts acylation of anisole withchloroacetyl chloride. Either polar or non-polar hydrophobic solventscan be used.

Compositions

The esters of carboxylic acid agrochemicals described herein can beincorporated into useful agrochemical compositions. The esters aretypically formulated as emulsifiable concentrates in organic solvents oras suspension concentrates. In several cases, the emulsifiableconcentrate formulations of the dicamba esters provide equal or superiorpost-emergent control of broadleaf weeds as compared to thediglycolamine salt of dicamba, while greatly reducing dicambavolatility. In addition, improved pre-emergent control of broadleafweeds can be achieved. The 2,4-D esters are significantly less solublethan dicamba esters, however, and are therefore typically formulated assuspension concentrates.

The compositions of the esters of carboxylic acid agrochemicalstypically comprise one or more adjuvants. Typical adjuvants include, butare not limited to, solvents, surfactants, dispersants, antifreezeagents, antifoam agents, thickeners, bacteriostats, wetting agents,dyes, and combinations or mixtures thereof.

The solvent may comprise, for example, an aromatic hydrocarbon,monochlorobenzene, a naphthalenic organic solvent, isophorone, acarboxylic acid esters, a carboxylic acid diesters, a pyrrolidone, or acombination or mixture thereof.

Typical surfactants include nonionic surfactants and anionicsurfactants, and typically a mixture of a nonionic surfactant and ananionic surfactant is used. Typical surfactants include, but are notlimited to, ethoxylated alkyl alcohols, ethoxylated vegetable oils(e.g., ethoxylated castor oil), sulfonates (e.g., an alkylbenzenesulfonate calcium salt), or a combination or mixture thereof.

Dispersants that are typically used in the ester compositions include,but are not limited to lignosulfonate, sulfonatednaphthalene-formaldehyde condensates, polymeric dispersants, or acombination or mixture thereof. Typical antifreeze agents include, butare not limited to, propylene glycol, glycerin, or a combination ormixture thereof. The antifoam agent is typically a silicone antifoamagent, but other antifoam agents may also be used. Typical thickenersinclude, but are not limited to, xanthan gum, silicas, clays, or acombination or mixture thereof.

For most applications, particularly for fungicides and post-emergentherbicides, the esters are typically formulated as emulsifiableconcentrates in agronomically acceptable organic solvents. The solventstypically have a flashpoint above 65° C. and reasonable solubility forthe ester. The choice of solvent depends on various factors, includingsolubility, other actives that may be included in the formulation, andcost. Typical solvents include naphthalenic organic solvents,isophorone, monochlorobenzene, carboxylic acid esters and diesters, andpyrrolidones. The use of a mixture of a nonionic surfactant, preferablyethoxylated alkyl alcohols or vegetable oils and an anionic surfactant,preferably a sulfonate, is typical for the emulsification system.Typically, the ester is present at a concentration of from about 20percent to about 50 percent in the emulsifiable concentrateformulations.

For pre-emergent herbicides, suspension concentrates are the typicalformulations. Relatively high-melting and water-insoluble esters such as2-nitrobenzyl, 4-methoxyphenacylmethyl, and 2-quinoxalinol esters (suchas 1a, 9, and 13a, respectively, for dicamba) are typically formulatedas suspension concentrates. The concentration of the ester particles inthe suspension concentrate formulations is typically about 20 percent toabout 50 percent.

Formulation of suspension concentrates of water-insoluble solids isknown in the art and is discussed in T. F. Tadros, Surfactants inAgrochemicals, pp. 133-82 (1995). The photo-labile esters of the presentinvention are typically milled to a mean particle size of from about 0.5to about 10 μm, more typically from about 1 to about 5 μm, for ease offormulation and in order to achieve efficient photo-release in thefield. Bead milling is the preferred milling method.

The particles are typically dispersed using a polymeric dispersant. Suchdispersants are known in the art and typically have a comb structurewith hydrophobic backbone. Hydrophilic “teeth” protruding from thebackbone can be anionic, such as maleic or acrylic acid salts ornonionic polyethylene oxide chains. Lignosulfonates are also typicaldispersants and have similar properties. The formulations also typicallyinclude an antifreeze, for example propylene glycol or glycerin, as wellas agents to raise viscosity such as xanthan gum, silicas or clays.Bacteriostats, antifoam agents, wetting agents, and dyes can also beadded to the formulation as appropriate.

An alternative approach for the formulation of pre-emergent herbicidesis micro-encapsulation of a solution of the photo-labile esters. In thiscase, high solubility esters such as 2 and 3 are typically used.

In various embodiments, the ester of a carboxylic acid agrochemical inthe composition is an ester of dicamba or 2,4-D. The compositions mayalso comprise one or more additional agrochemicals. For example, thecompositions may include a second agrochemical, such as a herbicide, afungicide, an insecticide, a plant health agent, or a plant growthregulator. In some embodiments, the second agrochemical is an herbicide,such as glyphosate or an agronomically acceptable salt or ester thereof.Thus, for example, in some embodiments, the ester of a carboxylic acidagrochemical in the composition is an ester of dicamba, and thecomposition further comprises glyphosate or an agronomically acceptablesalt or ester of glyphosate. In concentrate compositions, the glyphosateconcentration is typically about 200 grams acid equivalent (a.e.)/L toabout 400 grams a.e./L.

Determination of the Efficacy of Labile Esters

The efficacy of the photolabile esters can be assayed in vitro, or ingreenhouse or field experiments. A useful in vitro assay forpost-emergent activity involves photolysis of a dilute solution of theesters using simulated sunlight. This is conveniently achieved byphotolysis of a solution of the ester in an organic solvent which ismiscible with water and to which some water has been added. As describedin the Examples, photolysis in acetonitrile or tetrahydrofurancontaining 10% water by weight is effective. Low concentrations of theester should be used so that the entire volume is exposed to sunlight.Since the maximum extinction coefficient of the typical esters above 220nm is in the range of 1000-10,000 M⁻¹ cm⁻¹, a concentration of 0.1 mM iseffective. Photolysis in a quartz tube exposed to simulated or actualsunlight is a typical protocol.

Suspension concentrate formulations of photo-labile esters can bescreened in vitro for pre-emergent activity by a similar protocol. Thesuspension concentrate is typically diluted in water to a concentrationof about 0.1 mM and photolyzed in a quartz tube. The samples aretypically filtered before analysis.

The in vitro assay is a useful screening tool for esters andformulations and has proven generally effective at predicting greenhouseand field performance. Formulations of photo-labile esters ofagrochemicals can be tested under greenhouse and field conditions underthe same protocols used for other agrochemicals. However, as can be seenin the Examples below, esters such as the 4-methoxy and4-n-butoxyphenacyl methyl esters (9 and 10 in the case of dicamba),whose absorbance spectrum is predominantly in the ultraviolet range,perform worse in the greenhouse than in in vitro or field experimentsdue to screening of ultraviolet light by the greenhouse roof.

Similar assays can be performed using water instead of organic solvents.Because of the limited solubility of some esters in water, the assay isperformed at lower concentrations, e.g., 0.01 mM, as in the Examplesbelow. This assay can identify photo-labile esters, but is moreeffective in characterizing hydrolytically labile esters and rankingtheir rates of hydrolysis.

Emulsifiable and suspension concentrates of 1a, 2, 9, 13a, 14, 17, 30a,32a, and 36a have proven effective for the control of a number ofbroadleaf weeds in field testing, as have emulsifiable concentrates of 2and 10. These weeds include Sesbania macrocarpa, morning glory,velvetleaf, Palmer amaranth, fat hen, and sicklepod.

Use of the Esters

The esters of carboxylic acid agrochemicals described herein can be usedfor the controlled release of the carboxylic acid agrochemical. Inparticular, in various embodiments, the invention relates to a methodfor the controlled release of a carboxylic acid agrochemical comprisingexposing a photolabile ester of the carboxylic acid agrochemical tonatural light (e.g., sunlight) or artificial light (e.g., incandescentor fluorescent light). In other embodiments, the invention relates to amethod for the controlled release of a carboxylic acid agrochemicalcomprising exposing a hydrolytically labile ester of the carboxylic acidagrochemical to aqueous conditions (e.g., rainwater or irrigationwater).

The esters of carboxylic acid herbicides described herein can also beused to control unwanted plants. In various embodiments, such methodscomprise applying to the unwanted plants a herbicidal composition of thepresent invention comprising an ester of a carboxylic acid herbicide,for example, an ester of dicamba or 2,4-D. This may be accomplished, forexample, by diluting, as necessary, the emulsion concentrate orsuspension concentrate compositions described above to produce anapplication mixture, and applying the mixture to the unwanted plants.Such methods may further comprise applying a second herbicide to theunwanted plants, e.g., glyphosate or an agronomically acceptable salt orester of glyphosate. In various embodiments, the carboxylic acidherbicide is dicamba and the second herbicide is glyphosate or anagronomically acceptable salt or ester thereof. The second herbicide canbe applied to the unwanted plants before, concurrently with, or afterapplication of the ester of a carboxylic acid herbicide. As describedabove, in some embodiments, the ester of a carboxylic acid herbicide andthe second herbicide are combined into a single formulation prior toapplication to the unwanted plants.

Herbicidal Methods of Use

In herbicidal methods of the present invention, an application mixture(e.g., comprising a dilution of an ester of a carboxylic acid herbicideconcentrate composition of the present invention), typically comprisingfrom about 0.1 to about 50 g a.e./L herbicide, is formed and thenapplied to the foliage of a plant or plants or an area where plants areto be planted at an application rate sufficient to give a commerciallyacceptable rate of weed control. This application rate is usuallyexpressed as amount of herbicide per unit area treated, e.g., grams acidequivalent per hectare (g a.e./ha). Depending on plant species andgrowing conditions, the period of time required to achieve acommercially acceptable rate of weed control can be as short as a weekor as long as three weeks, four weeks or longer.

In some embodiments of the present invention, crop plants include, forexample, corn, peanuts, potatoes, soybeans, canola, alfalfa, sugarcane,sugarbeets, peanuts, grain sorghum (milo), field beans, rice,sunflowers, wheat and cotton. In certain embodiments, the crop plant isselected from the group consisting of soybeans, cotton, peanuts, rice,wheat, canola, alfalfa, sugarcane, sorghum, and sunflowers. In variousembodiments, the crop plant is selected from the group consisting ofcorn, soybean and cotton.

Crop plants include hybrids, inbreds, and transgenic or geneticallymodified plants having specific traits or combinations of traitsincluding, without limitation, herbicide tolerance (e.g., resistance tocarboxylic acid herbicides or other herbicides), Bacillus thuringiensis(Bt), high oil, high lysine, high starch, nutritional density, anddrought resistance. In some embodiments, the crop plants are resistantto carboxylic acid herbicides (e.g., dicamba and/or 2,4-D) and/or otherherbicides (e.g., glyphosate).

The application mixture comprising an ester of a carboxylic acidherbicide of the present invention can be applied prior to planting ofcrop plants that are susceptible to the carboxylic acid herbicide (e.g.,dicamba-susceptible or 2,4-D-susceptible crop plants not having a traitproviding tolerance to the carboxylic acid herbicide), such as, forexample, from about two to about three weeks before planting. Cropplants that are not susceptible to the carboxylic acid herbicide (e.g.,corn with respect to auxin herbicides), or transgenic or geneticallymodified crop plants having one or more traits providing tolerance tothe carboxylic acid herbicide typically have no pre-planting restrictionand the application mixture can be applied before planting such crops,at planting, pre-emergence (i.e., during the interval after planting ofthe crop plant up to, but not including, emergence of the crop plant) orpost-emergence to the crop plants. For example, the application mixturecomprising an ester of a carboxylic acid herbicide of the presentinvention can be applied at planting or post-emergence to the cropplants having a trait providing tolerance to the carboxylic acidherbicide to control weeds susceptible to the carboxylic acid herbicidein a field of the crop plants and/or adjacent to a field of the cropplants. In another example, in some embodiments of the presentinvention, an ester of a carboxylic acid herbicide of the presentinvention (e.g., an ester of dicamba or 2,4-D) is combined withglyphosate co-herbicide (or a salt or ester thereof) in the applicationmixture and the crop plant comprises a glyphosate-tolerant trait and thecrop plant is further either (i) a plant species not susceptible to thecarboxylic acid herbicide or (ii) comprises one or more traits providingtolerance to the carboxylic acid herbicide. Accordingly, suchembodiments are useful to control (i) glyphosate susceptible plants and(ii) glyphosate resistant volunteer crop plants and/or weeds that aresusceptible to the carboxylic acid herbicide growing in a field of (iii)crop plants tolerant to glyphosate and the carboxylic acid herbicide.

The application mixture comprising an ester of a carboxylic acidherbicide of the present invention can be applied pre-emergent orpost-emergent to the weeds. Applying pre-emergent to the weeds generallyrefers applying the application mixture formulation at any time duringan interval from about 40 days, from about 30, from about 25 days, fromabout 20 days, from about 15 days, from about 10 days, or from about 5days pre-emergence of the weeds. Applying post-emergent to the weedsgenerally refers to applying the formulation at any time during aninterval up to about 1 day after emergence, up to about 2 days afteremergence, up to about 3 days after emergence, up to about 4 days afteremergence, up to about 5 days after emergence, up to about 10 days afteremergence, up to about 15 days after emergence, or up to about 20 daysor longer after emergence of the weeds.

Weed control mentioned herein refers to any observable measure ofcontrol of plant growth, which can include one or more of the actions of(1) killing, (2) inhibiting growth, reproduction or proliferation, and(3) removing, destroying, or otherwise diminishing the occurrence andactivity of plants. Weed control can be measured by any of the variousmethods known in the art. For example, weed control can be determined asa percentage as compared to untreated plants following a standardprocedure wherein a visual assessment of plant mortality and growthreduction is made by one skilled in the art specially trained to makesuch assessments. In another control measurement method, control isdefined as a mean plant weight reduction percentage between treated anduntreated plants. In yet another control measurement method, control canbe defined as the percentage of plants that fail to emerge following apre-emergence herbicide application. A “commercially acceptable rate ofweed control” varies with the weed species, degree of infestation,environmental conditions, and the associated crop plant. Typically,commercially effective weed control is defined as the destruction (orinhibition) of at least about 60%, about 65%, about 70%, about 75%,about 80%, or even at least about 85%, or even at least about 90%.Although it is generally preferable from a commercial viewpoint thatabout 80-85% or more of the weeds be destroyed, commercially acceptableweed control can occur at much lower destruction or inhibition levels,particularly with some very noxious, herbicide-resistant plants.

Novel Photo-Labile Protecting Groups

It has also been discovered that 2-quinoxalinol, maleic hydrazide, andphthalhydrazide moieties can be used as photolabile protecting groups.These moieties can be used in a method for the photo-release of acompound, wherein the method comprises exposing the compound to naturalor artificial light, and the compound has been chemically modified tohave an ester linkage to a photolabile protecting group having one ofthe following structures:

EXAMPLES Example 1: Synthesis of the Acid Chloride of Dicamba

The reaction was performed in a 1-liter, 3-neck round-bottom flask witha mechanical stirrer. The flask was immersed in an oil bath that wasinitially at room temperature. In order to avoid loss of thionylchloride from the reaction mixture, a water-cooled reflux condenser wasattached to one neck of the flask and the other neck was plugged afterdicamba addition was complete. 323 g of thionyl chloride was added tothe flask and the oil bath heater was switched on with a setpoint of 80°C. 400 g of dicamba was added through one neck over about ten minutes.Evolution of HCl gas began during addition and subsided after about 90minutes. The reaction was continued for about an hour after gasevolution subsided. About 475 g of crude liquid product was recovered.

Two batches of crude dicamba acid chloride were combined in a 2-literflask that was connected to a vacuum distillation apparatus. The flaskwas insulated with glass wool and placed in a heating mantle. Heat wasapplied and a small (40 g) fore-run containing residual thionyl chloridewas discarded. Vacuum was then applied and the product distilled at 210°C., 220 torr (29.3 kPa). 793 g of product was recovered.

Example 2: Synthesis of the Acid Chloride of 2,4-D

The reaction was performed in a mechanically stirred 1-liter, 3-neckround-bottom flask. One neck was connected to a 500 ml, 3-neckround-bottom flask through a latex tube connected to a glass gasdispersion tube immersed in 350 g of 50% NaOH plus 150 ml of waterwithin the flask. The caustic flask was connected to vacuum through atube with a pinchcock clamp to control the vacuum.

The reaction flask was immersed in an oil bath that was not heatedinitially. 350 g of thionyl chloride was added and heating and stirringinitiated. 500 g of 2,4-D acid was added over 51 minutes.

The acid chloride was purified by vacuum distillation between 145° C.and 180° C. at pressure from 104 to 160 torr (13.9 to 21.3 kPa). 291 gof acid chloride was recovered from the distillation.

Example 3: Synthesis of the 2-Nitrobenzyl Ester of Dicamba, 1a, from theAlcohol

76.6 g of 2-nitrobenzyl alcohol (0.5 mol, Aldrich), 52.6 g oftriethylamine (0.52 mol), and 1.9 g of DMAP (Aldrich, 0.03 equiv.) werecombined with 200 ml of CH₂Cl₂ in a 1-liter flask equipped with astirbar. 119.7 g of dicamba acid chloride (0.5 mol). The mixture grewwarm over five minutes but no refluxing occurred.

After stirring for four hours, 20 g of NaHCO₃ in 300 ml of water wasadded in order to extract the DMAP and most of the ((CH₂CH₃)₃NH⁺)(Cl⁻)as well as free dicamba. The organic phase was separated and dried over10 g of MgSO₄. After filtration, the solvent was removed using a rotaryevaporator. The product precipitated in the flask. It was scraped out,rinsed with CH₂Cl₂ and methyl-t-butyl ether and dried overnight at 80°C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purge. 110.2 g wererecovered (62% yield).

Example 4: Synthesis of the 2-Nitrobenzyl Ester of Dicamba, 1a, Via2-Nitrobenzyl Chloride

99 g of 2-nitrobenzyl chloride (0.58 mol, Acros,), 127 g of dicamba (1.0equiv,), 58 g of triethylamine (1.0 equiv.), and 300 ml of CH₂Cl₂ werecombined in a 1-liter round-bottom flask equipped with a stirbar. Theflask was immersed in a 78° C. oil bath and refluxed for 18 hours with awater-cooled condenser attached. A white precipitate formed during thistime ((CH₂CH₃)₃NH⁺Cl⁻).

The reaction mixture was extracted with a solution of 10 g of NaHCO₃ in400 ml of water. The organic phase was isolated by decantation and aseparatory funnel and dried over 15 g of MgSO₄. After filtration, thesolvent was removed using a rotary evaporator. A heavy orangeprecipitate formed over about an hour. The solid was recovered byfiltration and rinsed with methyl-t-butyl ether to remove the orangecolor. The off-white solid was dried over a weekend at 55° C. under 24″Hg (81.3 kPa) vacuum with nitrogen purge. 126.1 g was recovered (0.35mol, 61%).

Compound 1c can be synthesized by methods similar to those describedabove for 1a, except that 3-nitrobenzyl alcohol or 3-nitrobenzylchloride is used as the starting material.

Example 5: Synthesis of the 6-Nitroveratryl Alcohol Ester of Dicamba, 1b

10.7 g of 6-nitroveratryl alcohol (0.050 mol, Alfa Aesar), 12.0 g ofdicamba acid chloride (1.0 equiv.), 1.0 equiv of triethylamine, 0.05equiv. of DMAP and 285 g of CHCl₃ were combined in an Erlenmeyer flask.Dissolution of the alcohol was incomplete. The mixture was stirred for70 hours, wrapped in foil.

After reaction, solution of 1.2 equivalents (6.3 g) of Na₂CO₃ in 100 mlof water was added to the mixture in order to hydrolyze unreacteddicamba acid chloride and extract it into water. The mixture was stirredfor 30-60 minutes and the organic (lower) layer was removed and thenwashed with 5 g of NaHCO₃ in 50 ml of water using a separatory funnel.The CHCl₃ solutions stirred over 10 g of MgSO₄ in order to removeresidual water. The MgSO₄ was filtered and the solvent removed on arotary evaporator.

The concentrate initially gave an oil, but a solid formed upon standingat room temperature. The suspension was rinsed into a fritted Buchnerfunnel using methyl-t-butyl ether, rinsed with more methyl-t-butylether, and transferred to a bottle. 13.0 g of a fine solid wasrecovered. The dark yellow filtrate was discarded.

The solid was dried under vacuum with nitrogen purge at 60° C. for threehours. 11.6 g of a fine yellow powder was obtained after drying (56% oftheoretical).

Example 6: Synthesis of the 2-Nitrophenethyl Ester of Dicamba, 2

49.8 g of 2-nitrophenethyl alcohol (Aldrich, 0.30 mol), 33.1 g oftriethylamine (1.1 equiv.), 74.9 g of dicamba acid chloride (1.05equiv.), 1.82 g of DMAP (5 mol %), and 150 ml of CH₂Cl₂ were combined ina 500-ml round-bottom flask equipped with a stirbar and stirredovernight at room temperature. Mild heat evolution was noted initially,but the solution did not boil.

After 15 hours, a heavy precipitate was observed. 15 g of Na₂CO₃ in 200ml of water was added to extract the precipitate (HN(CH₂CH₃)₃ ⁺Cl⁻) andhydrolyze residual dicamba acid chloride. The aqueous layer wasseparated and the organic layer washed with 12 g of NaHCO₃ in 150 ml ofwater to extract DMAP and residual organic salts. The organic layer wasthen dried over 10 g of MgSO₄, filtered, and concentrated on a rotaryevaporator. Crystallization occurred on cooling. The product wasrecovered by filtration, rinsed with methyl-t-butyl ether, and driedunder 24″ Hg (81.3 kPa) vacuum at 45° C. with nitrogen purge for twohours. 66 g of a light yellow crystalline solid was recovered (0.18 mol,60% yield).

Example 7: Synthesis of the 2-(2-Nitrobenzoxy)Ethanol Ester of Dicamba,4

20.64 g of 2-iodoethanol (0.12 mol, Aldrich), 13.4 g of triethylamine(1.1 equiv.), 28.7 g of dicamba acid chloride (1.0 equiv.), 0.73 g ofDMAP (0.05 equiv.), and 50 ml of dry CH₂Cl₂ were combined in around-bottom flask equipped with a stirbar. Mild heat evolution wasnoted immediately after adding the last component, DMAP.

After stirring for three hours, a solution of 5 g of Na₂CO₃ in 70 ml ofwater was added to extract (CH₂CH₃)₃NH⁺Cl⁻ and hydrolyze residualdicamba acid chloride. After stirring for an hour, 5 g of NaHCO₃ in 70ml of water was added and stirred briefly to extract DMAP. The yelloworganic phase was isolated using a separatory funnel and dried overMgSO₄. After filtration, the solvent was removed using a rotaryevaporator to a light orange low-viscosity residue (43.6 g, 97% oftheoretical).

The residue was dissolved in 50 ml of CH₂Cl₂ in a round-bottom flask.5.8 g of a 60% suspension of NaH in mineral oil was added. (1.2 equiv.with respect to 2-iodoethanol used in first step, Rohm and Haas viaAldrich). A solution of 18.4 g of 2-nitrobenzyl alcohol (1.0 equiv.,Aldrich) in 100 ml of CH₂Cl₂ was added over 26 minutes with a droppingfunnel. Light hydrogen evolution was observed initially. After fiveminutes, a heavy precipitate formed, hydrogen evolution acceleratedsignificantly, and the solution grew warm but never refluxed. From thistime forward, the solution began to darken.

The mixture was stirred for four hours. Then 8 g of NaHCO₃ in 100 ml ofwater was added to neutralize residual NaH. The mixture was then pouredinto a flask containing 450 ml of water in order to extract NaI andseparate the phases. More water had to be used to isolate the organiclayer because both phases were dark in color. Adding water lightened thecolor of the aqueous phase. The organic phase was dried over MgSO₄,filtered, and concentrated on a rotary evaporator. Diethyl ether wasadded, leading to the formation of a small amount of a gummyprecipitate. The product was filtered and the filtrate againconcentrated on a rotary evaporator. 30.0 g of a red-purple liquid wascollected (62% of theoretical).

Example 8: Synthesis of p-methoxy-α-chloroacetophenone and the4-methoxyphenacyl methyl ester of dicamba, 9

194.6 g of anisole (1.8 mol, anhydrous, Sigma), 169.4 g of chloroacetylchloride (1.5 mol, Sigma) and 250 g of CS₂ were combined in a 1-literflanged reaction vessel with a rounded bottom. The mixture wasmechanically stirred and 227 g (1.7 mol) of AlCl₃ was added over 12minutes.

After two hours of reaction, the reaction mixture was carefully pouredout into a 4-liter beaker containing 1.0 kg of ice and 650 g ofconcentrated hydrochloric acid. The mixture was agitated with a spatula.A light-colored precipitate formed as the red color was discharged. 200ml of CHCl₃ was used to rinse the reaction vessel and added to thebeaker, forming a separate organic layer on the bottom. The aqueouslayer was mostly decanted and the mixture was filtered. The water wasimmediately decanted from the filtrate. More product precipitated in thefilter flask and it was recovered in the same Buchner funnel as theoriginal precipitate. The precipitate was rinsed with ethyl acetate anddried overnight at 80° C. under 24″ Hg (81.3 kPa) vacuum with nitrogenpurge. 220 g were recovered.

150 g (0.81 mol) p-methoxy-α-chloroacetophenone prepared as above wasadded to a 1-liter round-bottom flask along with 197 g of dicamba acid(1.1 equiv), 90 g of triethylamine (1.1 equiv.) and 400 ml of THF. Themixture was refluxed in a 70° C. oil bath with a reflux condenserattached. Substantial solid formation was visible within 10 minutes andthe solution had set up, freezing the stirbar, within 20 minutes.

After 3.7 hours of stirring, the contents of the flask were poured intoa beaker containing a solution of 30 g of NaHCO₃ in 600 ml of water. Theflask was rinsed out with a little more water which was added to thebeaker. A dark lower organic layer formed along with a light-coloredaqueous layer. After standing for about ten minutes, a heavy whiteprecipitate formed.

The mixture was given at least an hour to complete precipitation. It wasthen recovered by filtration, rinsed with methyl-t-butyl ether, anddried overnight at 80° C. under 24″ Hg (81.3 kPa) vacuum with nitrogenpurge. 252 g were recovered (83%).

Example 9: Synthesis of the p-n-Butoxyphenacylmethyl Ester of Dicamba,10

100 g of n-butyl phenyl ether (0.68 mol, Aldrich), 73.2 g ofchloroacetyl chloride (0.95 equiv), and 200 g of CS₂ were combined in amechanically-stirred round-bottom reaction vessel equipped with awater-cooled condenser. 100 g of AlCl₃ (1.1 equiv.) was added over 10minutes with stirring. Refluxing began after 3 minutes and subsidedafter 20 minutes. Stirring was continued for a total of two hours.

The reaction mixture was carefully poured out onto a mixture of 900 g ofice and 400 g of conc. HCl. The mixture was stirred with a spatula toensure complete hydrolysis, then extracted twice with diethyl ether (250and 150 ml). The diethyl ether extracts were stirred for 30 minutes with100 g of conc. HCl. The ether layer was then separated and stirred witha solution of 15 g of Na₂CO₃ in 200 ml of water to remove HCl andresidual chloroacetic acid. It was again separated and dried over 20 gof MgSO₄.

110.1 g of liquid product was recovered and combined with 1.0 equivalentof triethylamine and dicamba in THF in a round-bottom flask equippedwith a reflux condenser. The mixture was stirred for 15 hours in a 75°C. oil bath. A solution of 15 g of NaHCO₃ in 300 ml of water was addedand stirred briefly, leading to phase separation.

The dark organic phase was separated and washed with 300 ml of water.Roughly 100 ml each of CH₂Cl₂ and water were added and stirred toimprove phase separation. The organic layer was isolated and the solventremoved using a rotary evaporator. 179 g were recovered (0.44 mol, 90%yield if pure).

Example 10: Synthesis of the 2-Quinoxalinol Ester of Dicamba, 13a

73.1 g of 2-quinoxalinol (0.5 mol, Aldrich), 1.2 g of DMAP (0.02equiv.), 120 g of dicamba acid chloride (1.0 equiv.), 53.1 g oftriethylamine (1.0 equiv.) and 300 ml of anhydrous CH₂Cl₂ were combinedin a 1-liter round-bottom flask. A vigorous reaction ensued, withrefluxing occurring within about two minutes and the formation of ayellow color. Refluxing subsided after about 20 minutes. The solubilityof 2-quinoxalinol was initially poor, but after 30 minutes the productappeared to be dissolved and the white suspended solid appeared to be(CH₃CH₂)₃NH⁺Cl⁻.

The reaction mixture was stirred for three hours. 15 g of NaHCO₃ in 300ml of water was then added to extract (CH₃CH₂)₃NH⁺Cl⁻, DMAP, andunreacted dicamba acid chloride. The organic layer was isolated anddried over 35 g of MgSO₄. The solution was filtered and the solventremoved with a rotary evaporator. The solid was recovered by filtration,rinsed with ethyl acetate and diethyl ether to remove the orange color,and dried at 60° C. under 24″ Hg (81.3 kPa) vacuum with hydrogen purge.116.0 g of a colorless, crystalline solid was recovered (0.33 mol, 66%yield).

Compound 13b can be synthesized in a similar manner, using3-methyl-2-quinoxalinol as the starting material.

Example 11: Synthesis of the 2-Hydroxypyridine Ester of Dicamba, 14

52.1 g of 2-hydroxypyridine (0.55 mol, Alfa Aesar), 55 g oftriethylamine (1.0 equiv.), 2.0 g of DMAP (3 mol percent), and 131.1 gof dicamba acid chloride (1.0 equiv.) were combined with 100 ml ofCH₂Cl₂ in a round-bottom flask equipped with a stirbar. The solutionimmediately took on a yellow color and boiled vigorously within a minuteas heavy white solid precipitated, freezing the stirbar. Boilingsubsided within five minutes.

The mixture was held without heating for two hours and then added to asolution of 35 g of NaHCO₃ in 500 ml of water to extract unreacteddicamba, DMAP, and (CH₂CH₃)₃NH⁺Cl⁻. The organic layer was separated andconcentrated on a rotary evaporator without vacuum. Crystallization of ayellow solid began immediately afterwards. The solid was recovered byfiltration, rinsed with acetone and methyl-t-butyl ether and driedovernight at 80° C. under 24″Hg (81.3 kPa) vacuum with nitrogen purge.105.3 g were recovered (64% yield).

Example 12: Synthesis of the Maleic Hydrazide Diester of Dicamba, 17

11.2 g of maleic hydrazide (0.10 mol, Sigma Aldrich) and 54 g of dicambaacid chloride (2.2 equiv) were combined with 100 mL of pyridine in around-bottom flask equipped with a stirbar. The reaction mixture wasinitially lemon yellow with white suspended solid. Heat evolutionoccurred immediately.

The reaction mixture was stirred for four hours. A solution of 30 g ofNa₂CO₃ in 300 ml of water was added in order to neutralize anyhydrochloride salt of the product and extract pyridine into the aqueousphase. A liquid lower red phase separated initially but a fine whitesolid crystallized beginning in about half an hour. The mixture wasstirred overnight to complete crystallization. The solid recovered byfiltration and rinsed with water and methyl-t-butyl ether. The solid wasthen dried at 90° C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purge.Yields varied from 68-84%.

Example 13: Synthesis of the Phthalhydrazide Diester of Dicamba, 18

8.3 g of phthalhydrazide (0.05 mol, Sigma Aldrich) and 27 g of dicambaacid chloride (2.2 equiv.) were combined with 50 ml of pyridine in around-bottom flask equipped with a stirbar. Heat evolution occurredimmediately along with the formation of a homogeneous orange solution. Aprecipitate began to form after 11 minutes.

The reaction mixture was stirred overnight (17 hours) and added to asolution of 15 g of NaCO₃ in 120 ml of water to neutralize anyhydrochloride salt of the product and extract pyridine into the aqueousphase. Heavy precipitate persisted. The mixture was stirred for twohours, then filtered. The solid was rinsed with water and methyl-t-butylether and dried at 90° C. under 24″ Hg (81.3 kPa) vacuum with nitrogenpurge. 18.7 g of the diester, a light yellow powder, were recovered (66%of theoretical).

Example 14: Synthesis of the 2-Nitrobenzyl Ester of 2,4-D, 5a

26.4 g of 2-nitrobenzyl bromide (0.11 mol, Acros) was combined with 26.4g of 2,4-D (1.05 equiv), 11.5 g of triethylamine (1.0 equiv.) and 100 mlof dry THF in a 250-ml round-bottom flask. The mixture was refluxedovernight in a 73° C. oil bath with a water-cooled condenser attached,then poured into a flask containing 15 g of NaHCO₃ in 150 ml of water. Awhite solid precipitated.

The solid was recovered by filtration, rinsed with deionized water, anddried under 24″ Hg (81.3 kPa) vacuum with nitrogen purge at 85° C. 40.4g were recovered (nearly quantitative).

Example 15: Synthesis of the 4-Methoxy-Phenacylmethyl Ester of 2,4-D, 11

18.5 g of p-methoxy-α-chloroacetophenone from Example 8 was added to a500 ml round-bottom flask equipped with a stirbar along with 24.3 g of2,4-D (1.1 equiv), 11.1 g of triethylamine (1.1 equiv.), and 150 ml ofTHF. A water-cooled reflux condenser was attached and the flask wasimmersed in a 80° C. oil bath.

The mixture was refluxed for 19 hours with stirring at which time afinely divided white solid was seen in the flask, a mixture of productand (CH₂CH₃)₃NH⁺Cl⁻. 10 of NaHCO₃ in 150 ml of water was then added todissolve the (CH₂CH₃)₃NH⁺Cl⁻ and extract unreacted 2,4-D andtriethylamine. A little CO₂ bubbling was seen, suggesting that sometriethylamine had volatilized out. The suspension was filtered,recovering a white product. The solid was rinsed with diethyl ether anddried at 80° C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purge. 17.7g of white solid was recovered (48%).

Example 16: Synthesis of the 2-Quinoxalinol Ester of 2,4-D, 15a

29.2 g of 2-quinoxalinol (Aldrich), 20.2 g of triethylamine (1.0equiv.), 0.73 g of DMAP (0.03 equiv.), 55.1 g of 2,4-D acid chloride(1.15 equiv), and 200 ml of dry CH₂Cl₂ were combined in a 500-mlround-bottom flask equipped with a stirbar. Dissolution of the2-quinoxalinol was only partial. Mild heat evolution was observedimmediately.

After 16 hours, the solution was still heterogeneous. 10 g of NaHCO₃ in150 ml of water was added and stirred in order to dissolve(CH₂CH₃)₃NH⁺Cl⁻ and extract dicamba and DMAP. The off-white solid wasrecovered by filtration, rinsed with water, methanol, and diethyl ether,and dried under 24″ Hg (81.3 kPa) vacuum with nitrogen purge at 80° C.33.6 g were recovered (45% of theoretical).

Example 17: Synthesis of the Bromoxynil and Ioxynil Esters of Dicamba,23b and 23c

This Example describes the synthesis of the bromoxynil and ioxynilesters of dicamba. For the bromoxynil ester, 10.4 g of3,5-dibromo-4-hydroxybenzonitrile (“bromoxynil,” 38 mmol, Acros) wascombined with 0.2 g of DMAP (5 mol %), 3.8 g of triethylamine (1.0equiv.), 50 ml of CH₂Cl₂, and 9.9 g of dicamba acid chloride (1.1equiv.) were combined in a round-bottom flask equipped with a stirbar.The mixture was stirred at room temperature for 4.5 hours before, asolution of 4 g of NaHCO₃ in 60 ml of water was added to hydrolyzeresidual dicamba acid chloride and extract (CH₂CH₃)₃NH⁺Cl⁻, dicamba, andDMAP. After stirring for an hour, a fine white solid was isolated byfiltration, rinsed with methyl-t-butyl ether, and dried overnight at 70°C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purge. 11.65 g of a purewhite powder was recovered (65% of theoretical).

The ioxynil ester was prepared using the same procedure, combining 11.8g of 3,5-diiodo-4-hydroxybenzonitrile (“ioxynil,” 32 mmol, Acros), 0.2 gof DMAP (5 mol %), 3.2 g of triethylamine (1.0 equiv.), 50 ml of CH₂Cl₂,and 8.4 g of dicamba acid chloride (1.1 equiv.). The mixture was stirredfor 22 hours before adding a solution of 4 g of NaHCO₃ in 60 ml ofwater. Considerable suspended solid was present which was recovered byfiltration after an hour of stirring. The solid was dried for five hoursat 80° C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purge. 11.7 g ofa pure white fine solid was recovered (64% of theoretical).

The chloroxynil ester of dicamba (23a) can be prepared in a similarmanner, using 3,5-dichloro-4-hydroxybenzonitrile (“chloroxynil”) as thestarting material.

Example 18: Synthesis of the 4-Methoxybenzyl Ester of Dicamba, 29a

138.2 g of 4-methoxybenzyl alcohol (1.0 mol, Aldrich) was combined with102 g of triethylamine (1.0 equiv.), 2.4 g of DMAP (2 mol %), 200 ml ofacetonitrile, and 264 g of dicamba acid chloride (1.1 equiv.). Themixture turned dark red and grew very hot, but did not boil. Heavyprecipitate had accumulated within an hour. The mixture was stirred for3.6 hours and then added to 60 g of NaHCO₃ in 800 ml of water in orderto hydrolyze and extract residual dicamba acid chloride and extractacetonitrile, DMAP and (CH₂CH₃)₃NH⁺Cl⁻. The product separated as a darklower layer. The aqueous layer was decanted and washed with 500 ml ofwater. It was then concentrated on a rotary evaporator. 358.1 g ofproduct was recovered as a low-viscosity liquid (105% of theoretical).

Example 19: Synthesis of the 4-Methoxyphenol Ester of Dicamba, 30a

112 g of 4-methoxyphenol (0.9 mol, Alfa Aesar), 91 g of triethylamine(1.0 equiv.), 1.1 g of DMAP (3 mol percent), and 216 g of dicamba acidchloride (1.0 equiv,) were combined with 600 ml of CH₂Cl₂ in a 2-literErlenmeyer flask equipped with a stirbar. Boiling and formation of awhite precipitate began. After 11 hours of stirring, 40 g of NaHCO₃ in800 ml of water was added to extract (CH₂CH₃)₃NH⁺Cl⁻ and DMAP. Theorganic phase was isolated using a separatory funnel and the solventremoved with a rotary evaporator. The product was poured into a beakercontaining 100 ml of hexane. Crystallization of the product as a whitesolid began upon cooling. The solid was recovered in a Buchner funnel,washed with hexane, and dried at 50° C. under 24″ Hg (81.3 kPa) vacuumwith nitrogen purge. 280 g of product was recovered as a fine whitecrystalline powder (95% of theory).

Example 20: Baylis-Hillman Condensation of Ethyl Acrylate with Ortho,Meta, and Para-Nitrobenzaldehyde and Synthesis of the Dicamba Esters,31a, 31b, and 31c

100 g of the nitrobenzaldehyde (0.66 mol, Alfa Aesar) was combined with80 g of ethyl acrylate (1.2 equiv., Alfa Aesar), 4.5 g of DABCO (6 mol%), and ethanol in a 500-ml flask equipped with a stirbar. The mixtureswere stirred for six days. 20 g of NaHCO₃ in 250 ml of water was addedin order to neutralize and extract DABCO along with most of the solventand acrylate. A lower organic layer separated which was isolated, driedover 25 g of MgSO₄, and concentrated on a rotary evaporator. Theproducts were yellow-orange liquids. Conversion of the aldehydes wascomplete, but a small amount of residual ethyl acrylate was seen by ¹HNMR.

100 g of the three products (0.40 mol) was combined with 1.5 g of DMAP(3 mol %), 40 g of (CH₂CH₃)₃N (1.0 equiv.), 100 ml of CH₂Cl₂, and 95 gof dicamba acid chloride (1.0 equiv). Mild heat evolution was observedfor the ortho isomer, while the meta and para isomers exhibited mildboiling. A precipitate formed in all three flasks within 30 minutes. Themixtures were stirred overnight (19 hours) at which point the threereaction mixtures were gelatinous. 20 g of NaHCO₃ in 500 ml of water wasadded and the aqueous layer was decanted. Another 500 ml of water addedto extract residual (CH₂CH₃)₃NH⁺Cl⁻ and DMAP. The organic layer wasisolated and concentrated on a rotary evaporator. The products wereviscous liquids. ¹H NMR and FTIR confirmed the identity and purity ofthe three esters.

Example 21: Synthesis of Dicamba Ester 32a Via Michael Addition ofMethyl Vinyl Ketone to Maleic Hydrazide

101 g of maleic hydrazide (0.90 mol, Alfa Aesar), 85 g of methyl vinylketone (1.2 mol) and 650 ml of absolute ethanol were combined in a1-liter flask equipped with a stirbar. 0.5 g of 50% NaOH was added. Theflask was immersed in a 100° C. oil bath with a reflux condenserattached. After 7 hours of reaction, as shown in the table below, thehomogeneous mixture was poured out into an Erlenmeyer flask and chilledat about 5° C. for about three hours. A heavy white precipitate formedwhich was recovered by filtration rinsed with methyl-t-butyl ether anddried at 70° C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purgeovernight. 141 g of product was recovered (86% of theoretical).

170 g of the Michael addition product (0.93 mol) was combined with 94 gof triethylamine (1.0 equiv.), 600 ml of CH₂Cl₂, and 235 g of dicambaacid chloride (1.05 equiv) in a 2-liter flask. The mixture boiled andturned yellow within a minute as heavy precipitate formed, freezing thestirbar. It was allowed to stand for 16 hours before a solution of 50 gof NaHCO₃ in 600 ml of water was adding, dissolving almost all of theprecipitate. The mixture was filtered and the organic layer was isolatedand concentrated on a rotary evaporator. 325 g of the product wasrecovered as a viscous yellow liquid (90% of theoretical).

Example 22: Synthesis of Dicamba Ester 33a Via Michael Addition ofAcrolein to Maleic Hydrazide

39.2 g of maleic hydrazide (0.35 mol, Alfa Aesar), 25.8 g of acrolein(0.46 mol, Aldrich) and 200 ml of absolute ethanol were combined in a500 ml flask equipped with a stirbar. 0.5 g of 2.5N NaOH was added. Theflask was immersed in a 90° C. oil bath with a water-cooled refluxcondenser attached. The mixture was refluxed for two hours, at whichpoint a heavy precipitate was seen in the flask. The mixture was allowedto cool and the solid recovered by filtration. The product, a whitepowder, was rinsed with methyl-t-butyl ether and dried at 80° C. under24″ Hg (81.3 kPa) vacuum with nitrogen purge. 53.7 g were recovered (91%of theoretical). The ¹H NMR (CDCl₃) showed the product to be highly pureand entirely in the hemiaminal form.

33.6 g of the Michael adduct (0.20 mol) was combined with 0.5 g of DMAP(2 mol %), 20 g of triethylamine (1.0 equiv.) 250 ml of CH₂Cl₂, and 53 gof dicamba acid chloride (1.1 equiv.). Reaction ensued immediately withthe mild boiling and formation of a yellow color. After stirringovernight (16 hours), the mixture was combined with 30 g of NaHCO₃ in400 ml of water and stirred for about 20 minutes. The pale yelloworganic layer was isolated and concentrated on a rotary evaporator. Apale yellow, viscous liquid was recovered and placed in an 80° C. vacuumoven for 7 hours under 24″ Hg (81.3 kPa) vacuum with nitrogen purge.81.3 g were recovered (110% of theoretical).

Example 23: Synthesis of Dicamba Ester 34a Via Michael Addition ofAcrylonitrile to Maleic Hydrazide

44.8 g of maleic hydrazide (0.40 mol, Aldrich), 23.3 g of acrylonitrile(0.44 mol, Aldrich) and 300 ml of absolute ethanol were combined in a500 ml flask equipped with a stirbar. 8 drops of 2.5N NaOH were added.The flask was immersed in a 100° C. oil bath and a reflux condenserattached. After 14 hours of reaction, the mixture was filtered hot toremove some suspended white solid. Precipitation of a white solid fromthe filtrate began immediately thereafter. The flask was allowed tostand in a cold room to complete precipitation.

The solid was recovered by filtration and dried at 80° C. under 24″ Hg(81.3 kPa) vacuum with nitrogen purge. In order to clean up residualwater and eliminate the sodium salts, the product was suspended in amixture of 10 g of acetic acid and 75 ml of water and stirred briefly.The solid was recovered by filtration, rinsed with methyl-t-butyl etherand acetone, and dried at 80° C. under 24″ Hg (81.3 kPa) vacuum withnitrogen purge. All of the dry product (7.06 g, 43 mmol) was combinedwith 4.3 g of triethylamine (1.0 equiv), 0.16 g of DMAP (3 mol %), 100ml of CH₂Cl₂, and 11.3 g of dicamba acid chloride (1.1 equiv.) in aroundbottom flask equipped with a stirbar.

After 15 hours of stirring, 6 g of NaHCO₃ in 80 ml of water was added tothe cloudy solution. A small amount of white solid remained, which wasfiltered off, and the organic layer was isolated and concentrated on arotary evaporator. 11.2 g of a viscous, light yellow liquid wasrecovered, but a good deal of material remained in the flask. Botheventually crystallized and were recovered by filtration and rinsed withCH₂Cl₂. The off-white powder was dried at 80° C. under 24″ Hg (81.3 kPa)vacuum with nitrogen purge.

Example 24: Synthesis of Dicamba Ester 36a

100 g of 2,2,6,6-tetramethyl-3,5-heptanedione (0.54 mol, Alfa Aesar) wascombined with 50 g of cyanoacetamide (1.1 equiv.), 12 g of piperazine(0.25 equiv), and 300 ml of absolute ethanol in a 1-liter roundbottomflask equipped with a stirbar. A reflux condenser was attached and theflask was refluxed in a 90° C. oil bath overnight (15 hours).

The mixture was then added to a solution of 40 g of NaHCO₃ in 600 ml ofwater in order to protonate the piperazine and extract excesscyanoacetamide. The product separated as a clear upper layer which wasisolated. The water layer was rinsed with 200 ml of methyl-t-butyl etherwhich was isolated and combined with the product. The organic phase wasdried over 25 g of MgSO₄, which was then filtered and rinsed withadditional methyl-t-butyl ether. The filtrate was concentrated on arotary evaporator. 130 g was recovered (102% of theoretical).

All of the product was combined with 55 g of triethylamine (1.0 equiv.if pure), 1.3 g of DMAP (2 mol %), 100 ml of CH₂Cl₂, and 149 g ofdicamba acid chloride (1.15 equiv.) and stirred at room temperature for3 hours. Mild heat evolution was noted and a heavy white precipitateformed within ten minutes. After five hours of reaction, 30 g of NaHCO₃in 350 ml of water was added. After stirring for a few minutes theorganic layer was separated and the solvent removed on a rotaryevaporator. 225 g of product was recovered as a dark liquid (95% oftheoretical).

Example 25: Synthesis of a Pyridione Diester of Dicamba, 37a

42 g of 2-cyanoacetamide (0.5 mol, Alfa Aesar) and 53 g of benzaldehyde(1.0 equiv., Alfa Aesar) and 1.3 g of 50% NaOH were dissolved in 200 mlof absolute ethanol (enough for complete dissolution at roomtemperature) in a 3-neck roundbottom flask equipped with a stirbar. Agas dispersion tube was inserted through one side neck, the other sideneck was plugged, and a water-cooled reflux condenser was attached tothe center neck. The flask was immersed in a 90° C. oil bath andrefluxed for 2.5 hours. 50 g of additional cyanoacetamide was then addedalong with another 100 ml of ethanol. 1 hour after the secondcyanoacetamide addition, gentle air bubbling was initiated.

After a further 1.5 hours of reaction (5 hours total), 1.0 g of copperacetate monohydrate (1 mol %) in 5 g of acetic acid were added with afew ml of ethanol used to rinse it into the flask. The acetic acidneutralized the base in order to promote cyclization and to maintain thesolubility of the copper. Refluxing was continued for a further 2 hours(7 hours total). The reaction mixture was then poured out into a flaskand allowed to cool. The viscous liquid was placed in a vacuum oven at80° C. under 24″ Hg (81.3 kPa) vacuum with nitrogen purge to removeresidual ethanol and acetic acid. The resulting material, still highlyviscous, was transferred to ajar. 120 g was recovered (101% oftheoretical).

The product was placed in a 100° C. oven in order to melt it, and 34.7 g(0.15 mol) was transferred to a 1-liter roundbottom flask equipped witha stirbar. 0.5 g of DMAP (3 mol %) was added along with 33 g oftriethylamine (2.2 equiv.), 250 ml of CHCl₃, and 77 g of dicamba acidchloride (2.2 equiv.). The flask was immersed in a 75° C. oil bath and awater-cooled reflux condenser was attached. The condensation productinitially formed a sticky mass in the bottom of the flask but thesolution was homogeneous and stirring well with reflux within 20minutes.

After 4.5 hours of reaction, the mixture was added to a solution of 15 gof NaHCO₃ in 300 ml of water. The organic layer was separated, washedwith deionized water, and concentrated on a rotary evaporator. 97 g of adark, viscous liquid was recovered (103% of theoretical). The ¹H NMR wasconsistent with the assigned structure.

Example 26: In Vitro Testing of Dicamba Photo-Release from Photo-LabileDicamba Esters (Tetrahydrofuran Solvent)

This Example describes in vitro testing of dicamba photo-release byhomogeneous solutions of photo-labile dicamba esters. The esters weredissolved in tetrahydrofuran (THF). Ester concentration was 0.1 mM. 25ml of the solution was transferred to 22 mm tubes fabricated from gradedseal quartz tubing with a 19/22 tapered seal at the top, which wasclosed with a tapered glass plug and secured with a plastic ring clamp.The solution was entirely below the quartz-to-glass transition, ensuringthat the entire volume was exposed to the full spectrum.

The sealed tubes were placed in a Growth Chamber where they were exposedto simulated sunlight for 14 hours per day at 35° C. Dicambaconcentrations in the solution were measured during the course of thephotolysis. As seen below, several esters undergo near-quantitativeconversion to dicamba over a period of several days.

The results below, obtained using THF as a solvent, demonstrate highconversion of the photo-labile esters to dicamba. A sample of theinitial solution was reserved in a glass vial away from the light sourceand analyzed at the conclusion of the study, providing a measurement ofthe amount of dicamba present without illumination of the photolysissolution (the “dark control”).

Conversion to dicamba Dark Control 1 2 3 5 7 9 11 12 15 Ester % dicambaday days days days days days days days days  1a 1% 22% 33% 47% 66% 76% 2 0% 46% 54% 72% 84% 88% 98% 96% 95%  9 1% 76% 91% 90% 89% 89% 10 8%16% 15% 16% 19% 20% 29% 35% 35% 13a 11%  28% 35% 43% 48% 61% 66% 68%

Example 27: In Vitro Testing of Dicamba Photo-Release from Photo-LabileDicamba Esters (Acetonitrile/10% Water Solvent)

This Example is another photolysis of photo-labile dicamba esters, butusing acetonitrile containing 10% water by weight as the solvent. Theexperimental protocol is otherwise the same as in Example 18.

Conversion to dicamba Dark Control 1 2 3 5 7 11 13 15 19 Ester % dicambaday days days days days days days days days  2 0% 33% 56% 75% 93% 104% 107%  108%  96% 106%  10 8% 17% 19% 20% 24% 28% 32% 31% 32% 33% 14 0% 6%  9% 10% 12% 12% 19% 21% 25% 26%

Example 28: Emulsifiable Concentrate Formulations of Photo-Labile Estersof Dicamba

This Example describes formulation of photo-labile esters of dicamba asemulsifiable concentrates. In all cases, the emulsification system wasbased on a combination of a castor oil ethoxylate, typically SURFONICCO-54 from Huntsman, and an alkylbenzene sulfonate calcium salt,typically either NANSA EVM/2E, also from Huntsman or WITCONATE P1220EHfrom Akzo Nobel. Aromatic 200 solvent from Exxon (a complex mixture ofaromatic hydrocarbons) was used except in the case of the phenacylmethylester whose low solubility made it preferable to use monochlorobenzene,and in the case of 4-n-butoxyphenacymethyl, for which no solvent wasused. The formulations and their designations are shown in the tablebelow.

Ester Ester Surfact. Ester type ID wt % Solvent^(†) Surfact. 1^(‡) 2*2-nitrobenzyl  1a 15% A 200 P1220, 5% CO54, 5% 2-nitrophenethyl 2 15% A200 P1220, 5% CO54, 5% 2-(2-nitrophenoxy)ethanol 3 61% A 200 P1220, 5%CO54, 5% 2-(2-nitrobenzoxy)ethanol 4 63% A 200 P1220, 5% CO54, 5%4-methoxyphenacymethyl 9 10% MCB P1220, 5% CO54, 5%4-n-butoxyphenacymethyl 10 90% None P1220, 5% CO54, 5% 2-quinoxalinol13a 17% A 200 P1220, 5% CO54, 5% ^(†)A200 = Aromatic 200, MCB =monochlorobenzene ^(‡)P1220 = WITCONATE P-1220 EH *CO54 = SURFONIC CO-54

Example 29: Efficacy of Photo-Labile Ester Formulations forPost-Emergent Control of Velvetleaf

The efficacy of some photo-labile ester formulations from Example 28 forpost-emergent control of velvetleaf was tested in the greenhouse. Allformulations were tested at rates of 140, 280, 420, and 560 g dicambaequivalent per hectare rates and compared to the diglycolamine salt ofdicamba (CLARITY®) at the same rates and untreated control plants. Thevelvetleaf plants were 10-15 cm in height at the time of spraying.Percent control was evaluated three weeks after treatment. Theunderperformance of the 4-methoxy and 4-n-butoxyphenacyl esters in thesedata was likely due to screening of ultraviolet light in the greenhouse.Other esters were competitive with conventional salts of dicamba.

% Control of velvetleaf Ester type Ester ID 140 g/ha 280 g/ha 420 g/ha560 g/ha Diglycolamine salt — 44% 63% 68% 83% 2-nitrobenzyl 1a 46% 60%75% 73% 2-nitrophenethyl 2 50% 69% 78% 90% 4-methoxyphenacymethyl 9 23%19% 28% 29% 4-n-butoxyphenacymethyl 10 23% 33% 28% 33%

Example 30: Efficacy of Photo-Labile Ester Formulations forPost-Emergent Control of Velvetleaf

The methodology of Example 29 was used to evaluate the efficacy ofseveral photo-labile esters of dicamba for post-emergent control ofvelvetleaf as emulsifiable concentrate formulations described in Example28.

% Control of velvetleaf Ester type Ester ID 140 g/ha 280 g/ha 420 g/ha560 g/ha Diglycolamine salt — 54% 86% 96% 96% 2-(2-nitrophenoxy)ethanol3 36% 57% 40% 43% 2-(2-nitrobenzoxy)ethanol 4 32% 52% 50% 51%2-quinoxalinol 13a 44% 69% 70% 83%

Example 31: Emulsifiable Concentrate Formulations of Photo-LabileDicamba Esters Reduce Volatility Injury to Dicamba-Sensitive Plants

This Example demonstrates that emulsifiable concentrate formulations ofphoto-labile dicamba esters reduce volatility injury todicamba-sensitive plants compared to the use of dicamba salts underconditions which closely mimic field application. In this case, thediglycolamine salt of dicamba (CLARITY®) was used for comparison.

Dicamba photo-labile ester formulations from Example 28 were mixed witha commercial glyphosate formulation (ROUNDUP POWERMAX®) and diluted toprovide a solution with a 0.5% dicamba equivalent concentrate of theester (or dicamba diglycolamine salt) and 1.5% concentrate ofglyphosate. The mixtures were sprayed at a 10 gallon per acre (93.5liters per hectare) rate on soil in a plastic container (“humidome”)with a transparent lid. One soil container was sprayed with water as acontrol. Four glyphosate-tolerant, dicamba-sensitive soy plants betweenV2 and V3 stage were immediately placed on the sprayed soil and thedomes attached to the trays with binder clips. The soy plants were inpots placed directly on the soil but with aluminum foil wrapped aroundthe bottom to prevent uptake of dicamba or dicamba esters through theroots.

The closed containers were held for 24 hours in a growth chamber whichwas maintained at 35° C. with 40% relative humidity. The plants werethen removed and grown in a greenhouse for three weeks. At this timeplant injury and growth stage were assessed compared to the controltreated with water only.

Data from this experiment are given below. The use of photo-labileesters largely prevents the retardation of plant development asdetermined by growth stage while reducing plant injury compared todicamba salt formulations.

Ester type Ester ID % Injury Growth Stage Diglycolamine salt — 38% 62-nitrobenzyl  1a  8% 8 2-nitrophenethyl 2 13% 9 2-quinoxalinol 13a 18%8 Untreated —  0% 9

Example 32: An Emulsifiable Concentrate Formulation of Dicamba Ester 32aReduces Volatility Injury to Dicamba-Sensitive Plants

The method of Example 31 was used to assess the utility of ester 32a forreducing volatility injury compared to an aqueous dicamba salt solution,except that the dicamba and glyphosate acid equivalents were 0.6% and1.2% respectively, corresponding to application rates of 0.5 and 1.0lb/ac (0.56 and 1.12 kg/hectare). Ester 32a was formulated as anemulsifiable concentrate with 30% dicamba acid equivalent as shownbelow.

Ester 32a 52.3% Aromatic 200 (A 200) 42.7% NINATE 401-A* 3.5% STEPANTEXCO-40^(†) 1.5% *Alkylbenzene sulfonate (Stepan) ^(†)Castor oilethoxylate (Stepan)The average injury to soybeans 14 days after treatment was 19% fordicamba ester 32a versus 60% for the dicamba diglycolamine salt.

Example 33: Suspension Concentrate Formulations of Photo-Labile Estersof Dicamba

This Example shows how three dicamba esters of the present invention,1a, 9, and 13a, can be formulated as suspension concentrates whichundergo photo-release of dicamba over a period of several weeks whenexposed to sunlight. 1a and 13a underwent preliminary dry milling priorto dispersion, but this was unnecessary for 9. The esters were initiallydispersed in a solution containing the dispersing agents, antifoam, andantifreeze using a high shear mixer (Cowles dissolver). Size reductionwas then conducted using a horizontal bead mill with ceramic beads. Thexanthan gum thickener (KELZAN) was then added as a 1% solution in water.

All formulations contained 0.07% of a silicone antifoam (MAZU DF 100S)and 0.05% of a xanthan gum thickener (KELZAN). The loading of dicambaester was 35% (wt/wt) in all cases. The other components of theformulations are given in the table below. Water made up the balance ofthe formulation.

Mean Ester particle ID size Dispersant 1 Dispersant 2 Antifreeze  1a 3μm MORWET D425, 2.6% AGRILAN 755, 1.6% PG, 6.5% 9 8 μm SOKALAN CP-9,2.1% INVALON, 5.8% Glycerin, 11.9% 13a 3 μm PLURIOL ES8898, 2.6% EMULSONAG/TP1 3.3% PG, 6.5% Notes: PG = propylene glycol. AGRILAN 755 (AkzoNobel), SOKOLAN CP-9 (BASF), PLURIOL ES8898 (BASF) and EMULSON AG/TP1(Lamberti) are polymeric dispersants. MORWET D-425 (Akzo Nobel) andINVALON are sulfonated naphthalene-formaldehyde condensates.

Example 34: Efficacy of a Photolabile Ester of Dicamba in ReducingDicamba Volatility Under Realistic Agronomic Conditions

This Example illustrates the efficacy of photolabile in reducing thevolatility of dicamba under realistic agronomic conditions. Anemulsifiable concentrate of the 2-nitrobenzyl ester of dicamba, 1a, wasprepared using the Akzo Nobel surfactants SPONTO 334 and 336 along witha castor oil ethoxylated, SURFONIC CO-54, from Huntsman in Aromatic 200solvent. The composition is given below. The dicamba acid equivalentconcentration is 8.84%.

Component Weight % 2-nitrobenzyl dicamba ester, 1a 14.25% Aromatic 20080.75% SPONTO EC 334  2.25% SPONTO EC 336  2.25% SURFONIC CO-54  0.50%

The emulsifiable concentrate of 1a was combined with a commercialglyphosate formulation, ROUNDUP WEATHERMAX®, and sprayed on a test plotat a spray rate of 10 gallons per acre (9.35 liters per hectare). Theglyphosate and dicamba rates were 1.0 and 0.5 lb/acre (1.12 and 0.56kg/hectare) respectively on an acid equivalent basis. The test plot areawas approximately 0.05 acre (0.02 hectare) planted with soybeans thatwere then shortly before flowering. As a comparison, a mixture of thediglycolamine salt of dicamba (CLARITY®) and ROUNDUP WEATHERMAX wassprayed at the same rates.

Immediately after spraying, five air samplers were placed in the fourcorners and the center of the plots. Airborne dicamba was collected on apolyurethane foam (PUF) trap over the ensuing 24 hours and quantified.The maximum temperature during this period was 86° F. The averagedicamba level from the five samplers was 1.2 nanograms per cubic meterof air (ng/m³) compared to 11.1 ng/m³ for the diglycolamine dicamba saltcontrol formulation.

Example 35: In Vitro Testing of Dicamba Photo-Release and HydrolyticRelease from Dicamba Esters in an Aqueous Medium

This Example describes the determination of photo-lability andhydrolytic lability of dicamba esters in an aqueous medium. 1 mMsolutions of the esters were prepared in acetonitrile (or 0.05 mMsolutions of dicamba diesters). The solutions were then diluted withdeionized water to a concentration of 0.01 mM (or 0.005 mM fordiesters). The solutions were then transferred to quartz tubes and amberbottles and held in a growth chamber by the procedure of Example 26. A14-hour day was generally used at a constant temperature of 35° C.Hydrolytic activity was assessed by measuring the increase in dicambaconcentration after day zero in the amber (dark) bottles. In some cases,due to chromatographic conditions, some dicamba was seen at time zero,but this was an artifact. Photolysis manifested itself as increasedconversion in the quartz tubes compared to the dark control. The resultsof this testing, presented in the table below, show that these dicambaesters convert to dicamba partially or completely by a photochemicalmechanism.

Conversion to dicamba Day Day Day Day Day Day Day Day Day Day Day Ester0 1 2 3 4 7 10 11 14 21 28  1a Light 7% 13% 16%  8% 21% 29% 37% — 54%75% 107%  Dark 7%  8%  8%  8%  7%  8%  8% —  8%  8%  8%  2 Light 3% 78%79% 75% 77% 78% 84% — 82% 83% 86% Dark 3%  3%  3%  3%  3%  3%  3% —  3% 3%  3% 13a Light 8%  9% 12% 13% 13% 15% — 19% 20% — — Dark 8%  7%  7% 8%  8%  9% — 11% 12% — — 30a Light 6% — — 14% — — — — 23% 29% 36% Dark6% — —  5% — — — — 17% 17% 19% 32a Light 5% 14% 16% 18% 22% 27% — — 44%50% 59% Dark 5% 12% 14% 17% 22% 34% — — 41% 55% 70%

Example 36: In Vitro Testing of Dicamba Photo-Release and HydrolyticRelease from Dicamba Esters in an Aqueous Medium

This Example provides the results of an aqueous lability test followingthe protocol of Example 35 for several dicamba esters which convert todicamba primarily by hydrolysis. As shown by the results in the tablebelow, conversion of the dark controls generally equaled or exceededconversion in the photolysis solutions.

Conversion to Dicamba Day Day Day Day Day Day Day Day Day Day Ester 0 12 3 4 7 10 14 21 28 14 Light  2% 61% 63% 64% 68% 67% — 71% 71% 75% Dark 2% 68% 81% 84% 86% 92% — 90% 91% 97% 17 Light  6% 18% 26% 33% 36% 42% —53% — — Dark  6% 16% 26% 35% 41% 49% — 60% — — 29a Light 27% 75% 74% 75%74% 76% — 77% — — Dark 27% 81% 83% 83% 80% 84% — 85% — — 31a Light 16%45% 48% 46% 45% 46% 50% 51% 53% 53% Dark 16% 37% 43% 43% 44% 49% 50% 51%49% 50% 33a Light 13% 18% 20% 19% 22% 23% 30% 42% 53% 57% Dark 13% 15%18% 18% 22% 21% 28% 37% 50% 55% 34a Light  3% 10% 14% 16% 20% 29% — 48%60% 71% Dark  3%  9% 14% 18% 23% 38% — 56% 71% 87% 35a Light 19% 57% 58%58% 62% 60% — 64% 63% 65% Dark 19% 66% 69% 68% 71% 74% — 70% 70% 74% 36aLight 20% 57% 60% 58% 59% 63% — — 65% — Dark 20% 59% 61% 60% 60% 65% — —66% —

Example 37: Efficacy of Photo-Labile Ester Formulations forPost-Emergent Control of Velvetleaf

The methodology of Example 29 was used to evaluate the efficacy ofseveral esters of dicamba which convert to dicamba by hydrolysis forpost-emergent control of velvetleaf as emulsifiable concentrateformulations The efficacy of esters which undergo rapid hydrolysis (suchas 14, 29a, and 35a) is similar to that of the glycolamine salt, butslower hydrolyzing esters such as (32a and 33a) exhibit reducedpost-emergent efficacy.

% Control of velvetleaf Ester ID 140 g/ha 280 g/ha 420 g/ha 560 g/haDiglycolamine salt 43.3% 65.8% 87.5% 90.0% 14 40.0% 58.3% 80.8% 85.0% 1723.3% 41.7% 75.0% 73.3% 29a 30.0% 55.0% 74.2% 81.7% 30a 19.2% 12.5%18.3% 15.0% 32a 12.5% 19.2% 33.3% 37.5% 33a 15.8% 27.5% 22.5% 30.8% 35a35.8% 60.0% 85.0% 87.5% 36a 15.8% 26.7% 32.5% 66.7%

Example 38: Field Testing of Emulsifiable Concentrate Formulations ofDicamba Esters 1a, 2, 9, and 13a

Four dicamba esters, 1a, 2, 9, and 13a, were formulated as emulsifiableconcentrates for field testing. All formulations contained 5% each of aalkylbenzene sulfonate calcium salt (Huntsman NANSA EVM 62/H or AkzoNobel WITCONATE P-1220 EH) and castor oil ethoxylate (Huntsman SURFONICCO-54) as the emulsifiers and Aromatic 200 (Exxon) or monochlorobenzene(MCB) as the solvent. The formulations are given in the table below.

Ester Ester wt. % Solvent^(†) Surfactants^(‡) Dicamba ae*  1a 11.9% A200, 78% P1220/CO54 7.4% 2 20.6% A 200, 69% P1220/CO54 12.3% 9  9.9%MCB, 80% EVM62H/CO54 5.9% 13a 13.6% A 200 76% EVM62H/CO54 8.6% *Dicambaacid equivalent ^(†)A200 = Aromatic 200, MCB = monochlorobenzene^(‡)P1220 = WITCONATE P-1220 EH, CO54 = SURFONIC CO-54, EVM62H = NANSAEVM 62/H

The esters were compared to the diglycolamine salt of dicamba (CLARITY™)for post-emergent control of three broadleaf weeds: velvetleaf, morningglory, and hemp sesbania. Rates of 280 and 420 g dicamba acid equivalentper hectare were used. Nitrophenyl esters 1a and 2 were equivalent tothe dicamba salt for post-emergent control of all three types of weeds.Phenacylmethyl ester 9 and quinoxalinol ester 13a were equivalent to thedicamba salt for post-emergent control of morning glory and hempsesbania, and were nearly equivalent to the dicamba salt forpost-emergent control of velvetleaf. Evaluations were conducted at 11 or21 days after treatment. Locations and timing were identical for allformulations tested.

Ester Velvetleaf Morning glory Hemp sesbania % control, 280 g/ha DicambaDGA salt 87 100 81  1a 86 100 95 2 85 94 92 9 79 98 86 13a 72 100 95 %control, 420 g/ha Dicamba DGA salt 91 100 88  1a 92 98 98 2 92 95 97 980 100 93 13a 84 100 98

Example 39: Field Testing of Dicamba Esters 1a, 9, 13a, 15, and 17 inthe Southern Hemisphere

Five dicamba esters (1a, 9, 13a, 14, and 17) were tested in the fieldfor post-emergent activity in the Southern Hemisphere. The primary weedswere Euphorbia species. Ester 9 was tested as a suspension concentrateusing the formulation of Example 33 The other esters were tested asemulsifiable concentrates having the formulations shown in the tablebelow. Akzo Nobel SPONTO EC 334 and SPONTO EC 336 along with SURFONICCO-54 and NANSA EVM 70/2E (Huntsman) were used as emulsifiers andAromatic 200 (A 200; Exxon) was used as the solvent.

Ester Ester wt. % Solvent (A 200) ^(†) Surfactants^(‡) Dicamba ae*  1a14.3% 81% EC334, 2.3%  8.8% EC336, 2.3% CO54, 0.5% 13a 17.1% 78% EC334,2.3% 10.8% EC336, 2.3% CO54, 0.5% 14 17.2% 73% EVM70/2E, 5%, 12.8%CO-54, 5% 17 18.0% 72% EVM70/2E, 5%, 15.4% CO54, 5% *Dicamba acidequivalent ^(†) A200 = Aromatic 200 ^(‡)EC334 = SPONTO EC 334; EC336 =SPONTO EC 336; CO54 = SURFONIC CO-54; EVM70/2E = NANSA EVM 70/2E

The results of field tests at rates of 0.25 and 0.50 lb dicamba acidequivalent (a.e.) per acre (0.28 and 0.56 kg dicamba a.e. per hectare)are given in the table below. The diglycolamine salt of dicamba(CLARITY™) was used as a comparator.

% control, 0.25 lb/ac % control, 0.50 lb/ac Ester (0.28 kg/hectare)(0.56 kg/hectare) DGA salt 53 70  1a 72 78  9* 54 62 13a 46 55 14 47 5617 41 53 *Suspension concentrate

Example 40: Field Testing of Emulsifiable Concentrate Formulations ofDicamba Esters 30a, 32a, and 36a

Three dicamba esters, 30a, 32a, and 36a, were formulated as emulsifiableconcentrates for field testing. All surfactants are commercial materialsfrom Stepan. The formulations are given in the table below.

Ester Dicamba Ester wt. % Solvent^(†) Surfactants^(‡) ae* 30a 50.0% MCB,45% TOXIMUL 8320, 5% 34% 32a 52.3% A 200, 43% NINATE 401-A, 3.5%, 30%STEPANTEX CO-40, 1.5% 36a 68.9% A 200, NINATE 401-A 2.5%, 35% 26.1%STEPANTEX CO-40, 2.5% *Dicamba acid equivalent ^(†)A200 = Aromatic 200,MCB = monochlorobenzene ^(‡)TOXIMUL 8320 is a butyl block copolymer,NINATE 401-A is an alkylbenzene sulfonate, and STEPANTEX CO-40 is acastor oil ethoxylate

The formulations were tested in the field. Locations and timing wereidentical for the three esters, but differed slightly for thediglycolamine control. The esters were compared to the diglycolaminesalt of dicamba (CLARITY™) for post-emergent control of three broadleafweeds: velvetleaf, morning glory, and hemp sesbania. Rates of 280 and560 g dicamba acid equivalent per hectare were used. Ester 36a, whichconverts rapidly to dicamba by hydrolysis has a post-emergent activitysimilar to the dicamba salt. Ester 30a, which converts relatively slowlyby photolysis is less efficacious. Ester 32a, which exhibits anintermediate conversion rate and ultra-low volatility in the closedhumidome assay, has an intermediate activity, as expected.

Ester Velvetleaf Morning glory Hemp sesbania % control 19 days aftertreatment, 280 g/ha Dicamba DGA salt 78 ± 10 89 ± 11 89 ± 5 30a 56 ± 2579 ± 7   50 ± 20 32a 59 ± 28 70 ± 24 76 ± 5 36a 72 ± 25 83 ± 4   82 ± 10% control 19 days after treatment, 560 g/ha Dicamba DGA salt 91 ± 7 94 ±12 96 ± 2 30a 65 ± 25 78 ± 10  67 ± 13 32a 68 ± 26 87 ± 10 91 ± 8 36a 84± 26 93 ± 5  98 ± 2

In view of the above, it will be seen that the several objects of theinvention are achieved and other advantageous results attained.

As various changes could be made in the above compositions and methodswithout departing from the scope of the invention, it is intended thatall matter contained in the above description and shown in theaccompanying figures shall be interpreted as illustrative and not in alimiting sense.

When introducing elements of the present invention or the preferredembodiments(s) thereof, the articles “a”, “an”, “the” and “said” areintended to mean that there are one or more of the elements. The terms“comprising”, “including” and “having” are intended to be inclusive andmean that there may be additional elements other than the listedelements.

What is claimed is:
 1. An ester of a carboxylic acid agrochemicalcomprising a labile protecting group and having the formula (XV):

wherein A represents the remainder of the carboxylic acid agrochemicalbonded to the carboxylic acid moiety; R₁ is an electron-withdrawinggroup; and wherein R₂ and R₃ are independently H or alkyl.
 2. The esterof a carboxylic acid agrochemical of claim 1, wherein the carboxylicacid agrochemical is a herbicide, a fungicide, an insecticide, a planthealth agent, or a plant growth regulator.
 3. The ester of a carboxylicacid agrochemical of claim 1, wherein the carboxylic acid agrochemicalis a herbicide selected from the group consisting of dicamba,2,4-dichlorophenoxyacetic acid (2,4-D), fenoxaprop, fenoxaprop-P,desmedipham, cyhalofop, carfentrazone, flufenpyr, fluthiacet,fluroglycofen, pyraflufen, flumiclorac,4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB), fluroxypyr, picloram,quinclorac, benazolin, clodinafop, 4-(2,4-dichlorophenoxy)butanoic acid(2,4-DB), 2,4,5-trichlorophenoxy acetic acid (2,4,5-T), dichlorprop,dichlorprop-P, diethatyl, endothall, fluazifop, flufenpyr, flumiclorac,fluoroglycofen, haloxyfop, indole-3-acetic acid, indole-3-butyric acid,mecoprop, mecoprop-P, pyrafluren, fenoprop, triclopyr, aminopyralid,bispyribac, chlorthal, imazamethabenz, pyrothiobac, quinmerac,quizalofop, quizalofop-P, diclofop, and lactofen.
 4. The ester of acarboxylic acid agrochemical of claim 1, wherein the carboxylic acidagrochemical is dicamba.
 5. The ester of a carboxylic acid agrochemicalof claim 1 wherein the carboxylic acid agrochemical is2,4-dichlorophenoxyacetic acid (2,4-D).
 6. The ester of a carboxylicacid agrochemical of claim 1, wherein the carboxylic acid agrochemicalis: a fungicide selected from the group consisting of benalaxyl andpicoxystrobin; a plant health agent selected from the group consistingof salicylic acid and 3,6-dichlorosalicylic acid; or a plant growthregulator selected from the group consisting of cloprop and4-chlorophenoxyacetic acid (4-CPA).
 7. The ester of a carboxylic acidagrochemical of claim 1, wherein the electron-withdrawing group isselected from nitriles, ketones, aldehydes, esters, carboxylates, andnitro.
 8. The ester of a carboxylic acid agrochemical of claim 1,wherein: R₂ and R₃ are both H; or one or both of R₂ and R₃ is alkyl,wherein the alkyl is optionally C₁-C₁₈ alkyl.
 9. The ester of acarboxylic acid agrochemical of claim 1, wherein R₁ is selected from thegroup consisting of —COCH₃, —CHO, —CN, and, —COOCH₂CH₃.
 10. The ester ofa carboxylic acid agrochemical of claim 1, wherein: R₁ is —COCH₃ and R₂and R₃ are both H; R₁ is —CHO and R₂ and R₃ are both H; R₁ is —CN and R₂and R₃ are both H; or R₁ is —COOCH₂CH₃ and R₂ and R₃ are both H.
 11. Theester of a carboxylic acid agrochemical of claim 1, wherein thecarboxylic acid agrochemical is dicamba or 2,4-dichlorophenoxyaceticacid (2,4-D) and the ester is selected from the group consisting of:


12. A composition comprising an ester of a carboxylic acid agrochemicalof claim
 1. 13. The composition of claim 12, which is in the form of anemulsifiable concentrate or suspension concentrate.
 14. The compositionof claim 12, further comprising one or more adjuvants selected from thegroup consisting of solvents, surfactants, dispersants, antifreezeagents, antifoam agents, thickeners, bacteriostats, wetting agents,dyes, and combinations or mixtures thereof.
 15. The composition of claim12, wherein: the solvent comprises an aromatic hydrocarbon,monochlorobenzene, a naphthalenic organic solvent, isophorone, acarboxylic acid ester, a carboxylic acid diester, a pyrrolidone, or acombination or mixture thereof; the surfactant comprises a mixture of anonionic surfactant and an anionic surfactant; the surfactant comprisesan ethoxylated alkyl alcohol, an ethoxylated vegetable oil, a sulfonate,or a combination or mixture thereof; the surfactant comprisesethoxylated castor oil, an alkylbenzene sulfonate calcium salt, or acombination or mixture thereof; the dispersant comprises alignosulfonate, a sulfonated naphthalene-formaldehyde condensate, apolymeric dispersant, or a combination or mixture thereof; theantifreeze agent comprises propylene glycol, glycerin, or a combinationor mixture thereof; the antifoam agent comprises a silicone antifoamagent; and/or the thickener comprises xanthan gum, a silica, a clay, ora combination or mixture thereof.
 16. The composition of claim 12,wherein the carboxylic acid agrochemical is dicamba or2,4-dichlorophenoxyacetic acid (2,4-D).
 17. The composition of claim 12,further comprising a second agrochemical.
 18. The composition of claim17, wherein the second agrochemical is an herbicide.
 19. A method forthe controlled release of a carboxylic acid agrochemical comprisingexposing an ester of a carboxylic acid agrochemical of claim 1 toartificial or natural light.
 20. A method of controlling unwanted plantscomprising applying to the unwanted plants an ester of a carboxylic acidagrochemical of claim 1.